On the upcoming ACAM-529 vaccine trial

November 13, 2013 |

[Eds: Please visit Bill’s new blog at http://liveherpesvaccine.com/]

David Knipe, Lynda Morrison, and Jeffrey Cohen are three of the principal scientists who have been involved in research over the past 15 years that has brought the HSV-2 ACAM-529 vaccine to a Phase I Clinical Trial.  Sanofi Pasteur is the company that has backed / sponsored the ACAM-529 vaccine, and Sanofi Pasteur will presumably be bringing the HSV-2 ACAM-529 vaccine to market if it succeeds in all phases of human clinical trials.

Dr. Knipe was kind enough to share the following information with me earlier today, which I pass along for those who may be interested in enrolling in the ACAM-529 vaccine clinical trial.


Hi Bill,

Here are the links for the start of the HSV5-29 trial for your blog.



If people want to write to me about the trial (I am not conducting it though), they can write to me at this address:  dknipe@hms.harvard.edu



something completely differentDavid, I believe that I speak for millions of genital herpes sufferers worldwide when I say thank you for your dedication and perseverance over the past 15 years, which has brought ACAM-529 from a HSV-2 vaccine concept to the first human clinical trial of a HSV-2 viral vaccine that has real potential to be a game-changer.

You have my best wishes and hopes that the trials of the HSV-2 ACAM-529 vaccine represent a turning point in the development of a HSV-2 genital herpes vaccine that is both safe and effective.

– Bill H.

198 Responses to On the upcoming ACAM-529 vaccine trial

  1. Ally January 3, 2015 at 8:12 am #

    Hi Bill,

    First of all, I really wanted to thank you for all your answers that are very precise and let us have an insight into the research going on on HSV.

    I am a bit confuse cause non english speaker and wanted to confirm that :

    The vaccine acam529 is aimed at stopping outbreaks and keep HSV-2 at a latent step forever.
    But will not completely kill and clear the body from this virus due to the fact that he is located very profoundly in our nervous system (DNA very alike with us).
    Is it correct?

    Thank you for your answer and I wish you a happy new year 2015.

  2. Ed Ra December 27, 2014 at 11:54 pm #

    Hi Bill Halford
    I was diagnosed with hvs-1 oral and genital about 6 months ago I was wondering if the vaccine acam529 is gonna work just in the genital area or also is gonna help about oral herpes I know that is the same virus hsv that’s affects both areas I’m a little confuse. Well the question is acam529 vaccine is gonna work for hvs-1 And hvs-2? Also does the vaccine is gonna help to all kinds of hsv1 oral, genital, herpes mat and hepes keratitis?
    First Thanks for made this website is the first web that I can get information to help me understand more about herpes also to know news about herpes and also thanks for all scientists, doctors etc to help to make a vaccine for herpes.
    Ill wait for you answer

  3. Life December 16, 2014 at 7:09 pm #

    Hi Dr. H. I’m interested in the vaccine or other working hsv vaccines. I read above briefly about others listed in this post that work. Waiting 5 more yrs for anything to come to trial is long. What other vaccines do you know provide relief? Anyone here can answer & share.
    Also are test persons still needed? I’d like to read the terms. I’m open. Thank you for your work. :)

  4. Vincent Deng November 28, 2014 at 4:57 am #

    Dear Dr.Bill

    I got the herpes for around 5 months, and the suffering from the neuralgia. Initially just few part of body like arm or leg, duration just few seconds. Until recent reccour, and everywhere on my body pain, the location not fix the duration also not fix. Is the virus eating my nerves? I recurred 4 times already, and the symptom is typical, but my HSV-2 IGG test is still negative. I feel helpless now. Could you help me to analyze my situation, and what should I do to eliminate the neuralgia? Sorry for my poor English.
    I am from China, the doctor here has few experience on this .thank you for your hardworking on vaccine.

    I wish every patients get well soon.

  5. Pritelivir November 7, 2014 at 4:12 pm #

    Hello Faith in God – Progress seems to take an eternity, however, activity has picked rapidly the last few years. Halford knows his viruses, and if you have taken the time to read through the voluminous questions and answers, you will understand why HSV529 and Immune Design’s viral fragment have a small probability of producing a robust immune response. Halford mutated one of the viral proteins numerous ways and discovered most produced less than robust responses. However, it appears one of the mutations produced a strong response.

    So, hopefully Halford will find the means to initiate a trial to demonstrate that his live, replication competent and attenuated vaccine either works or does not. But given that the Shingles vaccine is a mutated live virus, I see no reason why Halford’s vaccine will not work.

  6. Bill Halford November 7, 2014 at 1:40 pm #

    Hi Ed,

    I hear you loud and clear, but there are rules that dictate the path I need to follow. Doing what I can, as quickly as I can, but it just takes time. Hopefully, we can figure out a way to get some clinical trials going of a new live HSV-2 vaccine approach.

    – Bill H.

  7. Faith in God November 7, 2014 at 1:21 pm #

    Hi Pritelivir. I know progress is slow, but I hope Dr. Halford, gets to test his vaccine soon!! He seems to know what he is talking about, and seems to actually care. If we can test his live virus, it would show a growing and progressive step forward, where even if it proves unsuccessful, it will definitely be a step in the right direction and can provide invaluable research information. Although Bill is skeptical on Ian Frazers vaccine and Sanofi Pasteur-HSV 29 making moves such as what this article states. http://money.cnn.com/news/newsfeeds/articles/globenewswire/10102892.htm It can definitely provide different types of methods, to finally stabilize this bug.

  8. Ed November 2, 2014 at 11:12 am #


    Thankyou so so much for your reply. Have you tried your vaccine on humans yet and is it safe? If it is I know you don’t have the funding for trials, but could me and other people who have Hsv 2 try your vaccine? Even if I had to pay for it? It would change my life if it worked. I’m willing to try anything. Thankyou Bill

  9. Bill Halford November 2, 2014 at 8:18 am #

    Hi Ed,

    I do not have wild-type HSV-1 or wild-type HSV-2………but it has been a hobby / job / passion for the past 22 years.

    Will try to respond to the backlog of other comments in the next few weeks. I have been buried since returning from a 7-month sabbatical at the Rocky Mountain Laboratories in Hamilton, Montana.

    – Bill

  10. Ed November 1, 2014 at 10:05 am #

    Hi bill

    I subscribed to your blog awhile back and get an email every time someone replys on it! I’m always looking at this site!
    Anyway I did have a couple of questions for you…
    From a total of 9 ( I think ) vaccines in trial now can you see any of them working? If so why and which one?
    I really like the sound of your vaccine and I have recently been in contact with the ceo of AuRx who said there vaccine really worked and 49% of people who had 10-25 out breaks a year never had symptoms again. Is there vaccine similar to yours? Also Can I ask if you yourself have Hsv?
    Thankyou your time


  11. Bill Halford November 1, 2014 at 9:50 am #

    Dear Pritelivir, Faith in God, and all of the visitors to this blog,

    Please do not mistake my recent silence for either (1) a loss in interest or (2) disapproval / disagreement with what is being said. This could not be further from the truth. The wheels are in motion, but take time to turn. I arrived at the conclusion being offered here about 2 years ago, and have been working in the background trying to bring this idea into reality. Rest assured, I am on it. However, such matters take time, and it would counterproductive to the cause to discuss any details at this point in time.

    – Bill H.

    P.S. I always find it reassuring to remember that my own struggles are the same that have faced men and women for centuries before, time and time again, as exemplified in these lyrics from the Rush song “Vital Signs.”

    Leave out the fiction, the fact is this friction
    Will only be worn by persistence
    Leave out conditions, courageous convictions
    Will drag the dream into existence

  12. Pritelivir November 1, 2014 at 9:35 am #

    Bill – Faith in God is correct. After my experience with the AIC316 trial and watching a company trying to receive approval for a parathyroid hormone analog in the US for over a decade despite being approved by the EU, it is apparent the FDA is completely risk adverse. If there is a possibility of harm, no matter how low the probability, they will require a tremendous amount of proof through trials. More $ than most big pharmaceutical companies would be willing to invest. You need to go somewhere beyond the reach of the FDA if you expect to see your vaccine make it to market in your lifetime!

  13. faith in god November 1, 2014 at 1:32 am #

    Hello Dr. Halford! Much Respect to you, I admire you as a compassionate, human being. You’re a very empathetic individual. Just wondering, since you have issues with the FDA. Why don’t you attempt to take trials south of the border in Mexico??!! I would assume you wouldn’t need as much as money down there to pull off any research or assistance. You would NOT be under FDA regulations and you would help out MILLIONS AND MILLIONS of mean, I’m sure we can raise a lot of money on this blog alone. IDK, but 20 years of Politics and BS is too long. And once your vaccines proves effective, then Im sure you would get your Noble Prize as well as a great feeling of helping out so many people who physically and mentally SUFFER!! People would fly to Mexico to get vaccinated. Please do something. It sounds desperate but this is a difficult condition. I will help you with what I can. I’m an RN and Speak Spanish.

  14. BeaconStreet October 17, 2014 at 2:58 pm #

    Bill, any comments or reaction to the Sanofi-Immune Design development you can share with us? http://money.cnn.com/news/newsfeeds/articles/globenewswire/10102892.htm

  15. Manuel October 6, 2014 at 8:12 pm #

    I hope the vaccine have good progress to date, blessings for the people working on the project.

    Espero que la vacuna tengo buenos avances a la fecha, bendiciones para las personas que trabajan en el proyecto.

  16. Bruno September 25, 2014 at 9:36 pm #

    Hi Doctor Halford!

    I know you talked about, but there is a possibility of doing this trials in other countries? I do not understand much of it, but I think there are other countries where it is easier to perform the tests. Or is it more likely await the approval of the United States? Forgiveness for my English, is that I am from Brazil. Thank you for your commitment to the cause!


  17. Pritelivir September 20, 2014 at 5:40 pm #

    Bill – Prusiner’s account of the his progress was met with fierce opposition and animosity; everyone insisted prions has to have a nucleic core and would not budge from that dogma. Haldane’s four stages of progression are mentioned in the book along with many biological molecular explanations. Between your blog and Prusiner’s book, I now have a much better understanding of viruses and the immune system.

    Hopefully you will come up for air soon.

  18. Bill Halford September 20, 2014 at 4:32 pm #

    Hi Pritelivir,

    I will have to give this a look. Stanley Prusiner is credited with advancing the idea of prions (infectious proteins) such as are the root cause of Mad Cow Disease and a few other similar syndromes. Yes, everyone at the time thought Prusiner and others advancing the “prion hypothesis” were whack jobs, and then later on the scientific community gave him a Nobel Prize. The same story with Howard Temin in the 1960s who proposed that retroviruses (called RNA tumor viruses at the time) carried RNA in their virions and a reverse transcriptase to make a DNA copy of the RNA that could then be integrated into the host cell genome; HIV is a member of this family of viruses and Temin’s theory (based on the logical interpretation of the available evidence) proved to be 100% accurate. Still, at the time, Howard Temin’s “reverse transcription” theory was regarded as shite and madness by most of the so-called experts. Howard Temin and David Baltimore were jointly awarded the Nobel Prize 15 to 20 years later, and their work was instrumental in the development of two major classes of anti-HIV drugs.

    So, it goes in science. Most of the so-called experts are lemmings who all too easily recognize that someone’s theories differ from conventional thinking, but who are either unwilling or unable to evaluate the evidence being offered in support of a different theory.

    This is not a new phenomenon, and was described by a 19th century scientist, J.B.S. Haldane as such……….

    J.B.S. Haldane formulated the four stages of scientific acceptance:
    1. This is worthless nonsense.
    2. This is an interesting, but perverse point of view.
    3. This is true, but quite unimportant.
    4. I always said so.

    Established scientists sometimes enjoy positions of power that are predicated on the continued accuracy of a belief system or particular theory about how the natural world works. Lo and behold, when a change in theory is proposed, and threatens to change established scientists’ bottom line in terms of paycheck, grant-funding, future drug sales, or influence in science, the proposed new theory is not always greeted with open arms, but rather is often dealt with in a back room using a 9-mm pistol fitted with a silencer.

    All change is slow, and nowhere is this truer than a change in prevailing scientific beliefs.

    – Bill H.

  19. Pritelivir September 20, 2014 at 2:32 pm #

    Bill – I am reading Stanley Prusiner’s book, Madness and Memory, and I now understand the issues someone like yourself faces. I highly recommend it for people to grasp the difficulties face by researchers like that are breaking with tradition.

    Looking forward to reading your next post.

  20. Bill Halford September 20, 2014 at 2:14 pm #

    Thanks Jaclyn,

    Been meaning to post on therapeutic HSV-2 vaccines, but I teach a med school course for another 3 weeks, so another post will have to wait until then.

    – Bill H

  21. Jaclyn September 20, 2014 at 1:10 pm #

    Thanks for sharing your thoughts. I really appreciate your efforts and I
    aam waiting for your next post thnk you once again.

  22. Justin H August 22, 2014 at 11:42 pm #

    Hello Bill,

    This blog is great and thanks so much for the work you are doing. I just wish there was more funding for HSV research in general. HSV529 seems well-funded (private sector and NIH funding both, I think), is this because they talk about reducing HIV transmission risk by reducing HSV prevalence, and maybe using the same non-replicating vaccine development technique on viruses like HIV if it ends up being successful?

    I mean, I was just surprised how little the clinical trial summary actually talked about HSV itself. It makes me think that when we eventually have an HSV2 vaccine in 20 or 30 years, we’ll be calling it the “HIV Transmission Risk Reduction Vaccine (protects against HSV2, a known risk factor for HIV transmission)” . . . HSV529 seems like a science project for research good, and maybe it works, but not really focused on dealing with HSV as an “urgent” priority in and of itself . . . like they need to justify the effort by focusing on HIV, you know?

    Bill Gates and his foundation have given a lot of money to HIV research, have you run the numbers to see how cost-effective a live-attenuated HSV2 vaccine could be at preventing HIV acquisition in Sub-Saharan Africa and around the world? Your “boring” live vaccine (if it works) might actually be more cost-effective at reducing transmission risk than a lot of the other incremental options out there for preventing the spread of HIV . . . I mean, a bare bones basic vaccine that worked reliably and safely enough would be fantastic for “at risk” populations . . . most would agree.

    Maybe you could submit a proposal to the Gates Foundation directly for funding, basically showing in numbers and probabilities that the best way to fight HIV “right now” is by treating and preventing HSV2 cost-effectively in at risk populations . . . and arguing that you have a potential but “not yet tested in humans” way to do that cheaply and effectively if your live attenuated vaccine can get funding for testing . . . the Gates Foundation sometimes funds “under served” causes that traditional funding overlooks, and they do have a lot of cash, so maybe someone there might think of your vaccine as a novel approach to dealing with the HIV epidemic, since if it works on HSV2, it could really be a cost-effective way to save lives from HIV in the long run, and around the world in all sorts of far flung places – what do you think? Would the Gates Foundation take your call? Is direct private funding an option that would work to get trials going, at least in theory?

    Maybe they can roll the dice to test it without even putting up too much cash – as long as you agree to work with them to distribute it for extra-cheap in Africa or wherever they want, to help them fight HIV, if it ever works out?

  23. Jonbi August 22, 2014 at 6:33 pm #

    Hello Bill,

    It was recently discovered by a doctor that HSV-1 was the root cause of ME/CFS as well as a few other conditions.
    It was due to the immune system not being able to suppress the virus into latency.

    Currently, there is an antiviral compound suggested to force virus into latency. But that’s the best we have as of now.

    Is there anything else out there that you know of which can effectively treat/cure chronic HSV-1 ?

    Many thanks,

  24. Bill Halford August 22, 2014 at 4:53 pm #

    Hi BeaconStreet,

    What you are proposing makes sense from an abstract point-of-view, but fails to account for (1) the physical laws of nature and biology that say that your proposal is unrealistic and (2) the practical fact that your proposal is neither cost-effective, time-effective, nor possible.

    Rather than belaboring all of these issues, I will get to the bottom line……..what you are effectively saying is “Wouldn’t it be more effective if herpes sufferers were clairvoyant and could look into a crystal ball and find out if there was ABSOLUTELY NO RISK of transmitting their HSV infection to another person?” While I philosophically agree that this would be fabulous, it is unrealistic to think that such a crystal ball exists or is obtainable. Viruses are very small, and even the most sophisticated of research laboratories has a lower limit of detection for HSV-1, HSV-2, or any other virus by polymerase chain reaction (PCR). No scientist who knows what they are doing would ever say…..there is no HSV-2 in this patient’s sample; what they would say is that “HSV-2 DNA is not detectable, but may still be present, in this patient’s sample.” People who have HSV-2 will always have a risk of shedding the virus.

    For all of these reasons, a far more realistic way to eliminate the risk of transmitting “genital herpes disease” to a sexual contact is to have that contact immunized with a preventative HSV-2 vaccine. In principle, we have been stopping the spread of viral diseases in this manner for over 200 years. There is nothing magic about a preventative HSV-2 vaccine….it is very simple, and will work quite well, once we actually start testing the approach that is most likely to yield this desired outcome….a live-attenuated HSV-2 vaccine. I know that this approach is very boring, and lacks the pizazz of a crystal ball, but I note that a preventative HSV-2 vaccine would, unlike the other approach, actually achieve the desired result of shielding naive individuals in discordant relationships from the risk of acquiring genital herpes disease.

    – Bill H.

  25. BeaconStreet August 22, 2014 at 4:34 pm #

    Hi Doc: If cancers can be detected instantly at home, http://www.cbsnews.com/news/16-year-old-finds-a-new-way-to-detect-cancer/, why can’t there be a simple, fast and cost-effective at-home test to determine when HSV sufferers are asymptomatically shedding, and thus contagious? Wouldn’t a detection method, as opposed to treatment, also presumably have a faster path to FDA approval?

  26. BeaconStreet August 22, 2014 at 4:02 pm #

    Hi Doc: One of challenges with HSV, from a transmission and intimacy standpoint, is not knowing for sure when sufferers may be asymptomatically shedding (and thus contagious). The medical community’s been working on vaccine efforts for over thirty years, but do you know whether there’s ever been an effort to develop a simple, quick and cost-effective at-home test to determine days when transmission is possible? I would assume if shedding is occurring, there’s virus on the skin that should be detectable by some method. And perhaps a diagnostic method–as opposed to a treatment–would have a somewhat faster path to FDA approval.

  27. Ix July 22, 2014 at 1:09 am #

    Hi Bill,

    A year ago I began suffering from Meniere’s disease. Lately there has been much speculation about the origin of it and its relationship with HSV-1.

    Personally I have no doubt that there is a strong relationship between the two since the use of antivirals gets rid of my symptoms. I am also sure that this virus is much more evil than people think and causes far more pain than cold sores.

    I wonder if, in your opinion the HSV-529 vaccine may help people with this disease eliminating the (not so harmless) HSV-1 virus from our hearing systems.

    If not, are there any plans to develop a vaccine specifically for HSV-1?

    Thank you and best regards !

  28. Pritelivir July 20, 2014 at 2:51 pm #

    Below is a link that describes the conflict of interest between the FDA and Wall Street.


  29. Bill Halford July 20, 2014 at 1:45 pm #

    Hi Pritelivir,

    “Dallas Buyer’s Club” is a recent movie (drama) in which Matthew McConaughey played a guy from Texas who was diagnosed with AIDS at the beginning of the AIDS epidemic. The picture (and McConaughey) received several Academy Awards……very interesting and entertaining movie. It purports to depict the FDA in precisely the light you suggest as holding back anti-HIV drugs because it was in bed with the big pharma company behind AZT. As I said before, I think that more than a little creative license was taken with the facts of what actually happened in the 1980s to make the story interesting, and thus I have my doubts that things went down precisely as depicted.

    In general, when it comes to the FDA, I always favor the lowest common denominator explanations of (1) ineptitude and/or (2) lack of societal backbone to explain why the FDA holds drugs back for longer than is reasonably necessary. However, I cannot rule out your suggestion that big pharma companies are using FDA rules and processes to delay the entry of competitor drugs into the marketplace.

    – Bill H.

  30. Pritelivir July 20, 2014 at 11:46 am #

    Hey Bill,

    I have not heard of that show or documentary, will see if it available at the library.

    As far as AIC316 goes, I could not have said it better. When I was told of the hold and the reason for it, I immediately suspected GSK had something to do with it. Despite being off patent GSK continues to conduct trials for various complications in addition to hsv such hepatitis c.

    I could see the FDA putting a trial on hold if the trial would endure several months, but a four week trial? Either the side effects are much worse than is stated, which I do not believe, or someone wants to hold up the trial for monetary gain. Unfortunately not a single journalist, of the several I contacted, would go beyond searching on Google. So much for investigative journalism!

  31. Bill Halford July 20, 2014 at 1:47 am #

    Hi Pritelivir,

    Just finished watching the Dallas Buyer’s Club. I suspect the movie is a bit loose with the specific facts of when anti-HIV drugs became available in the 1980s. Nonetheless, it tells a story similar to what you have been posting on AIC-316 where the FDA appears to selectively back one drug, while delaying the advancement of a potential competitor drug, based on flimsy evidence.
    The FDA regulatory process has just grown too expensive and cumbersome and so the promising, new HSV helicase-primase inhibitor, AIC-316, appears to be taking forever to obtain FDA approval. Meanwhile, millions of people continue to live with the chronic diseases of genital herpes or oral herpes, both of which might be better managed with the assistance of AIC-316.
    At best, I think the FDA and our overly litigious society has forgotten that the risk of drug side-effects should be balanced against the amount of human suffering that occurs in the absence of a potentially effective drug. At worst, pharmaceutical companies that sell other anti-herpes meds may be encouraging the FDA to drag its feet so that they don’t have to compete with AIC-316. I am not a big conspiracy theorist, so I suspect that continued FDA/societal inability to realistically balance (1) drug risks versus (2) the medical complications of uncontrolled herpes is the more likely of the two explanations.

    – Bill H.

  32. Pritelivir July 19, 2014 at 11:28 pm #

    For anyone interested in AIC316 or Pritelivir, AiCuris replied to my email asking for a update on the hold status. Unfortunately the stated they have no updates and when they do it will be posted on their website.

    I can only interpret that as meaning they are having to conduct additional animal studies at ridiculous doses. After a more than a year of being put on hold by the FDA, AiCuris still can not free itself from the FDA’s lawyers.

  33. Bill Halford July 18, 2014 at 3:27 pm #

    Dear Libramale29,

    Thanks for the words of support, but I am not sure that I agree with your interpretation of where things stand in terms of “No one is coming forward when you (the Halford Lab) are providing the cure (for genital herpes).”

    What my laboratory has described is a live-attenuated HSV-2 vaccine. Traditionally (based on the past 220 years of history), scientists tend to think of vaccines as a means to prevent disease. Therefore, I would suggest that the most accurate way to think about a live-attenuated HSV-2 vaccine is as a tool that may be used to protect children and adolescents from facing the risk of acquiring wild-type HSV-2 later in life. I know that the concept of a “therapeutic vaccine” that could be used to cure genital herpes is very popular amongst sufferers, but I think it is important to appreciate that the past 220 years of history does not offer evidence, for or against, this concept. The idea of a “therapeutic HSV-2 vaccine” is a hopeful thought, and it remains a possibility, but that is all it is at the moment……a possibility that remains to be formally tested. Therefore, I would refrain from calling my lab’s live HSV-2 vaccine a cure…..this remains possible, but is at this juncture represents little more than speculation. Likewise, the data I have seen from the Agenus HerpV and Genocea GEN-003 therapeutic vaccine trials does not lead me to the conclusion that these approaches represent a “cure for genital herpes.”

    Regarding the suggestion that “no one is coming forward,” I note that this is a blog in a public forum where I discuss results that have already been obtained (in the past) and the current status of accepted knowledge. Please do not interpret my lack of discussion of my current, ongoing endeavors to mean that I have retired to the beach, and am spending my time surfing and drinking at the bar. Things are happening in the background, and my research is moving forward. I simply do not publicly discuss my research until I present at a scientific meeting and publish the results, and the lag time between starting and finishing a “published study” is generally 3 to 5 years.

    I recognize that many Americans have developed attention-deficit disorder, and believe that every question should be addressable on Google in about 30 seconds. I am here to tell you that research takes time and patience, and to progress from where we are now to a viable HSV-2 vaccine entering into the final phases of clinical trials is, at a minimum, a 10-year proposition. It is fine for the community of herpes sufferers out there to research, consider, and discuss every conceivable idea for a genital herpes cure. As a researcher, I cannot afford to do the same. I have to follow my instincts, identify what I believe is the most likely solution, and then be willing to spend 20 years investigating, developing, and explaining why the solution I am proposing is the most realistic and sustainable for the long haul of the next 1,000 years.

    Nothing I have published says my lab has identified a genital herpes cure, and the same is true for every researcher in the world. However, my research continues, and both myself and my graduate student have received predominantly positive comments when we have presented our results at numerous scientific meetings and research institutions over the past year.

    People are coming forward and agreeing with my lab’s HSV-2 vaccine findings, but this does not alter the fact that it will still take 10 – 20 years to put the ball across the goal line and expand our current vaccination regimens to include an effective HSV-1 and HSV-2 vaccine.

    – Bill H.

  34. libramale29 July 18, 2014 at 3:01 pm #

    Bill sorry to hear that no one is coming forward when u are providing the cure if I would have been there I would be the first person to come forward for this I request to the people to come forward and enroll else we will continuing waiting for the next post only nothing else

  35. Bill Halford July 18, 2014 at 12:13 pm #

    Hi Ed,

    One of many reasons that my laboratory chose to target the ICP0 gene when we made our live-attenuated HSV-2 vaccine is that the ICP0 protein is the lynchpin in the regulatory scheme that allows HSV-2 (and HSV-1) to “choose” between latency and reactivation. Although this may be a bit of an oversimplification, the available evidence indicates that HSV effectively “chooses” to establish latency (cease replication) by halting the production of two positive regulators, ICP0 and ICP34.5. Likewise, it appears that much of how HSV “chooses” to reactivate in latently infected neurons revolves around restoring the active expression of the ICP0 protein, which alters the HSV genome’s transcriptional program and “turns on” full blown viral mRNA synthesis again.

    Long story short……..ICP0 is both necessary and sufficient for efficient reactivation of latent HSV genomes (http://www.ncbi.nlm.nih.gov/pubmed/11238850; http://www.ncbi.nlm.nih.gov/pubmed/11390616).

    In practical terms, what all this means for a live HSV-2 vaccine is that my laboratory has spent the past 14 years building a compelling case that HSV-2 ICP0- mutant virus vaccines (1) should be incapable of reactivating in vaccine recipients and (2) are grossly impaired in their ability to cause disease in immunosuppressed animals (SCID mice) because these viruses are 800 times more sensitive to repression (control) by the body’s innate interferon system.

    On paper, Aurx and my lab’s live HSV-2 0NLS vaccine may be comparable in effectiveness. However, the data supporting the safety of my lab’s live HSV-2 0NLS vaccine is far more complete and compelling than what was published on Aurx. Finally, I note that active investigation of Aurx appears to have ceased more than a decade ago. It seems a bit unrealistic to assume that the laboratory staff who produced and studied the Aurx vaccine are sitting around at their laboratory benches waiting for Justin Bieber to drop $10 million in their lap so they can complete their studies.

    Finally, I note that the community of genital herpes sufferers are always suggesting that someone else (the government, Justin Bieber, Bill Gates) should provide the millions of support required to advance a HSV-2 vaccine that works through clinical trials. In reality, I don’t think genital herpes sufferers can have it both ways…….you cannot (1) hide in the shadows afraid to let society know genital herpes is a disease that has altered your life and at the same time (2) expect Bill Gates to step up to the plate and offer $100 million in support to solve a problem that is largely invisible to most of the world because it has no face and no voice. Magic Johnson was in the 1990s the face of AIDS…..the fact that such a great guy (and many others) was affected by this disease helped us all personify the problem, and see the importance of solving it.

    The way I see it, people in the genital herpes community can either (1) preserve their anonymity and wait for a cure to percolate out over the next 50 to 100 years, or they can (2) relinquish their anonymity and help educate the ~250 million Americans who don’t even realize that the genital herpes problem is not some vague black cloud off on the horizon. Rather, it is THEIR very own friends and relatives across the dinner table who have been silently suffering with the potentially isolating ramifications of this disease for years or decades.

    – Bill H.

  36. Bill Halford July 18, 2014 at 11:26 am #

    Hi Vaccinepromoter,

    Aurx is a live-attenuated HSV-2 vaccine bearing a mutation in the UL39 gene that encodes a protein known as ICP10, which functions in virus-infected cells as a ribonucleotide reductase. In simple terms, the live HSV-2 ICP10- mutant fails to replicate in neurons of the peripheral nervous system and that is why this HSV-2 virus is attenuated and may be used as a live HSV-2 vaccine. Laurent Aurelian and the group of investigators who developed this approach did so in the late 90s / early 2000s.

    My lab’s live-attenuated HSV-2 vaccine bears a mutation in the ICP0 protein, where ICP0 is effectively the “gas pedal” of a HSV-2 infection. Like a car with no gas pedal, HSV-2 ICP0- mutant viruses are fully functional……you can roll down the windows, listen to the stereo, turn on the engine, and even drive down the road…….but without a gas pedal, HSV-2 ICP0- mutant viruses don’t move very fast and certainly cannot outrun the cops of the body (i.e., the immune system). My lab described this live-attenuated vaccine approach in HSV-1 in 2006, and we showed that it could be translated to HSV-2 in 2010 and 2011. Now we are working on clarifying why this live-attenuated HSV-2 vaccine works 100 times better than the primary approach we have been testing in human clinical trials for the past 30 years……subunit vaccines that only expose the body’s immune system to ridiculously small pieces of HSV-2. GSK’s Herpevac vaccine, Agenus’s HerpV vaccine, and Genocea’s GEN-003 vaccine all fall into this “subunit vaccine” category. I suspect that the same is true of Corridon’s HSV-2 vaccine candidate, but have yet to read a full description of the underpinnings of this approach.

    Against that background, I don’t think a side-by-side comparison of Aurx versus my lab’s HSV-2 0NLS vaccine is the key missing puzzle piece at the moment. The key missing puzzle piece is that a grand total of n=0 human subjects have participated in large, organized, and government sanctioned clinical trials of a live-attenuated HSV-2 vaccine to date. Some may claim that HSV-2 ACAM-529 is a live-attenuated HSV-2 vaccine. Allow me to clarify why such assertions are incorrect. Traditionally, for the past 220 years, the “live vaccines” that successfully eradicated or controlled smallpox, polio, yellow fever, mumps, measles, rubella, chickenpox, shingles, and most recently rotavirus-induced diarrhea all contained “live viruses” that actively replicate (amplify themselves) and spread in recipients for several days after receiving the vaccine. ACAM-529 is a non-replicating virus, and thus is fundamentally different from the “live-attenuated vaccines” that have been successful in controlling viral disease.

    So, 220 years of history informs us that a bona fide live-attenuated HSV-2 vaccine would likely be adequate to stop the spread of genital herpes. What the scientific community has done with this information is (1) dubbed the approach dangerous based on not one drop of hard evidence and (2) never experimentally asked the question in even a single human being (i.e., n=0), “Is it possible that a live-attenuated HSV-2 vaccine would be more effective in a clinical trial relative to the subunit vaccines we have been testing for 30 years?”

    Therefore, I would suggest that for now, the more pressing question is whether (1) the Aurx or (2) the HSV-2 0NLS vaccine would be effective in human clinical trials? Based on my experience in science, I have yet to encounter a single experimental question that can be addressed based on n=0 tests. If we want to know if Aurx or HSV-2 0NLS would work as human vaccines, then we will need to test the concept in at least n=1 person, and perhaps the results would be even more compelling if we tested either vaccine in n=100 individuals. For purposes of comparison, more than 30,000 people in the U.S. were screened and/or enrolled in the most recent clinical trial of the Herpevac vaccine (Belshe, et al, 2012).

    – Bill H.

  37. Ed Harris July 18, 2014 at 11:02 am #

    I contacted Gary Calton who’s email address I got from aurx website. I asked if they were still looking for herpes funding. I got this response
    What that means is that the project is on hold. The big pharma’s want a large trial to make certain there are no liability issues, i.e., that no one can get the disease from the vaccine. Since everyone who is treated with the AuRx “therapeutic vaccine” will have the disease (and will have been tested for it), there is no danger. But to prove this, we need people who are committed with deep pockets. If they are infected, they will be committed if convinced by the small trial we ran — high placebo effect. It will take a minimum of $10 million, to be used in a Latin American country to set up the labs and run the trial.

    There are several celebrities who could fund this, but so far none has stepped up to the plate.

    On Thu, Jul 17, 2014 at 9:55 AM, Ed wrote:
    Not quite sure what you mean by that?!
    Is aurx still doing any work on a herpes vaccine? What is the latest?
    We are looking at staring up a website for donations on a large scale. Ie asking celebrities etc who ate known to have herpes to donate. Would you still be willing to accept a donation if we can get it together?


    Ed Harris

  38. Vaccinepromoter July 18, 2014 at 7:29 am #

    It would be awesome if Prof. Halford would test the AuRx vaccine against his vaccine.

    It could be easily obtained by contacting the scientists behind AuRx research.

  39. Ed July 17, 2014 at 11:24 am #

    Hi Dr Bill

    I’ve been reading through this who website in the past few weeks. I’ve got hsv2 and it’s completely destroyed my life. There’s not a day goes by where I don’t think about it. It’s made me so depressed almost to the point I wonder why I’m living. The only glimmer of hope I have is people like you. I just wanted to say thankyou and keep up the good work. A company called aurx was brought to my attention today. From what I read they had quite a good vaccine in the making, do you know much about this? Thankyou ed

  40. libramale29 June 24, 2014 at 8:34 am #

    Thanks bill for our response though I can’t sign the petition but I think you can have this linked to the website so many people who ate not aware can hit it and fill it also there are couple of forums where I will post that there is something they can contribute to and hopefully it will drive our aim BIll I wanted to ask you that since I m asymptomatic what are the chances if I always use a protection while having intercourse what are the chances for transmission to my partner the local docs are saying that its only possible to transmit when u have active sores can y please guide on this

  41. Looking for Serenity June 19, 2014 at 2:01 pm #

    Thank you for posting. I just sent off my letters and signed the petition.

  42. Thewayiam June 19, 2014 at 12:45 pm #

    Everyone concerned with the status of Pritelivir should try signing the petition I included on the link below. It was really fast and easy. I signed the petition and many others have as well. You can also select the feature to send “letter to congress”. It will take no time at all. Lets help spread the word.



    We can also start our on petition and try to get a few thousand signatures to back up our request

  43. Bill Halford June 16, 2014 at 6:43 pm #

    Hi Libramale 29,

    Based on what you describe, I simply don’t have adequate information to add to what your doctors have told you. All I can suggest is that you make sure that the doctor diagnosing you should be as much of an expert in infectious disease as you can find. With genital herpes, some cases are a slam dunk, and any doctor can make the diagnosis. However, in your case, it sounds like the facts are equivocal, and so you are essentially asking (I think)…..do I really have genital herpes or is there another explanation for my earlier symptoms? When people arrive at this question, my advice is always the same………..seek out an infectious disease specialist if this is an option for you. Don’t self-diagnose, and don’t ask a science geek his opinion over the internet. See a doctor (1) who seems trustworthy, (2) has a lot of common sense, and (3) who has plenty of experience diagnosing and treating infectious disease.

    – Bill H.

  44. Bill Halford June 14, 2014 at 12:07 am #

    Michael and Pritelivir,

    I provide a synopsis of where this stands below so that all readers may understand what you are discussing. Based on my limited knowledge of the specifics about this helicase-primase inhibiting drug, I agree with Pritelivir that the FDA needs to consider long and hard whether or not shelving this is a good idea based on toxicity in monkeys at 900x the relevant dose…..table salt and water are toxic if delivered in high enough doses by creative routes of administration. At more pharmacologically relevant doses in the relevant species (humans), the NEJM study concluded point blank that there were no adverse effects relative to placebo-treated controls.

    The synopsis is below.

    – Bill H.

    N Engl J Med. 2014 Jan 16;370(3):201-10. doi: 10.1056/NEJMoa1301150.
    Helicase-primase inhibitor pritelivir for HSV-2 infection.
    Wald, et al

    Participants who received the higher doses of pritelivir were less likely to have detectable HSV-2 compared with placebo recipients:
    o Placebo: HSV-2 shedding on 16.6% of days;
    o 5 mg daily pritelivir: 18.2% of days;
    o 25 mg daily pritelivir: 9.3% of days;
    o 75 mg daily pritelivir: 2.1% of days;
    The rate of adverse events was similar in all groups.

    In an accompanying editorial Richard Whitley and Mark Prichard from the University of Alabama at Birmingham noted that pritelivir represents a promising option for people with drug-resistant HSV and potentially for use in combination therapy combining drugs that work by different mechanisms.

    However, the U.S. Food and Drug Administration (FDA) has placed a hold on pritelivir due to signals of skin and hematological toxicity in monkeys given up to 900 times the doses tested in humans. Further investigation of the mechanisms underlying these toxicities is underway.

  45. libramale29 June 13, 2014 at 3:34 pm #

    Hey bill thanks for all of our work I have a question to u as I recently got the infection 4 months back initially I got the symptoms like burning in penis tip frequent urination testicals pains and that started after 2 or 3 days of acquring the virus after 3 months I see elevation in the hsv igg 1+2 combined test the titre level is 3.78 and the report says that if its below five its non reactive I still don’t have any genitals ulcers yes but some red rashes sometimes and some skin discoloration so what do u suggest I have it Or not how should I go ahead I know I can’t marry anyone now but the doctors ate saying that u have nothing by seeing the report is this possible that I only acquired few and not immune system killed all those and I m no more affected please advise

  46. Pritelivir June 13, 2014 at 6:08 am #

    That was the reason I was given. However, the level of anemia did not seem like an issue to the investigator in Indianapolis for a four week trial and was surprised by the FDA’s hold.

  47. Michael June 12, 2014 at 9:51 am #

    I was told by a prominent infectious disease specialist in Boston that the reason for shelfing this drug was that is caused anemia in monkeys.

  48. Pritelivir June 10, 2014 at 9:32 pm #

    Dr Halford – AIC316 has been given the name Pritelivir by AiCuris. I used the Freedom of Information Act to inquire the reason for the FDA’s Hold but was denied. I appealed but was denied again.

    Talk about dysfunctional; our entire health care system is in the same nut house. AIC316 is superior to Valtrex, as I can attest to. But taking 20 to 100 times the recommended dose may cause problems. How dumb is this country becoming? Try taking 20 to 100 aspirin, should we pull aspirin off the market?

    I am thoroughly disgusted with our health-care, government and most businesses entities. What happened to common sense?

  49. Bill Halford June 10, 2014 at 11:16 am #

    Dear Thewayiam,

    In my opinion, the reason that companies focus on HSV-2 vaccines (for starters) may be summarized as follows……….

    “Seroepidemiology indicates that 8 – 16% of the human population is infected with HSV-2. Between 0.5 and 1.1 billion people harbor persistent HSV-2 infections, and serve as a vast reservoir for the transmission of HSV-2 to future sexual partners. Ten to 20 million naïve individuals acquire new HSV-2 infections each year. The frequency of HSV-1 infection is higher; somewhere between 30 and 70% of the human population is infected with HSV-1, which means that 2 to 5 billion people carry HSV-1.
    HSV-2 is better adapted to complete its life cycle in the human genitalia. HSV-2 efficiently reactivates in sacral ganglia that innervate the genital region, and thus latent HSV-2 infections commonly cause recurrent genital herpes. Although HSV-1 accounts for one-third of cases of primary genital herpes, latent HSV-1 infection of the sacral ganglia is less likely to successfully reactivate and cause recurrent genital herpes. Thus, most vaccine efforts have focused on HSV-2 because it causes a larger burden of recurrent genital herpes.”

    If someone wants to develop a HSV-1 vaccine, no one is going to block such an effort. However, in my experience, there is a good reason that Viagara is one of the best-selling drugs of all time…….sex and sexual contact is an important part of how human beings relate to one another. If Viagara were Superman, then genital herpes would be kryptonite…..genital herpes impacts people’s sexuality, and more important it makes it incredibly uncomfortable for many people to ever enter into an intimate relationship again. Cold sores and oral herpes are a nuisance. Genital herpes and the prospect of being afraid to approach someone you would like to have an intimate relationship with can simply destroy some people’s reason for living.

    In my opinion, if you have to choose HSV-1 or HSV-2 (i.e., most problems are generally solved one at a time), HSV-2 is the logical place to start because it ruins the quality of life of a greater number of people. Not saying HSV-1 should never be solved, but if we have to prioritize and choose, I would suggest we start with HSV-2.

    – Bill H.

  50. Thewayiam June 10, 2014 at 10:53 am #

    One question I have. Why are all companies focusing solely on an HSV-2 vaccine when there are more people infected with HSV-1 orally and genetically? Wouldn’t it make sense to test both vaccines at once since the knowledge of how to potentially stop the spread exists already instead of just focusing on one type?

    As article was published just today and they seem to believe that an oral vaccine might work to prevent the spread of herpes. Sound interesting and promising. The article is entitled “PaxVax Signs R&D Collaboration with UC San Diego to Develop a Vaccine to Prevent Herpes Simplex Virus Infections”….ReDWOOD CITY, Calif. & SAN DIEGO, Jun 10, 2014 (BUSINESS WIRE) — PaxVax Inc., a specialty vaccine company with a commercial focus on travel and biodefense….

  51. Juggalo June 1, 2014 at 6:09 am #

    Your answer seems logical, but i do hope that the vaccine works like a therapy in high reactivators by not requiring an additional adjuvant.

  52. Bill Halford May 31, 2014 at 7:25 pm #

    Dear Juggalo,

    No, I don’t think viral vaccines require adjuvants for the reasons I detailed in my recent blot post entitled “How does the immune system respond to a HSV-2 vaccine?” Specifically, I wrote, “In the case of a whole HSV-2 vaccine (such as ACAM 529), the virus has its own pathogen-associated molecular patterns that provide the “danger signals.” Thus, whole HSV-2 viral vaccines generate their own pro-inflammatory / immune-activating signals, and do not require additional adjuvants such as alum or MPL.”

    The one exception to this rule is inactivated (dead) HSV-2 vaccines. There is good evidence (and a theoretical rationale) why an adjuvant would be useful / needed if one chose to go with an inactivated / dead HSV-2 vaccine. Personally, I would not advocate a dead HSV-2 vaccine because it lacks the metabolic capacity to efficiently stimulate one of the most important components of antiviral immunity……CD8+ T-cells. For this reason, a live HSV-2 vaccine makes more sense to me than an inactivated (dead) HSV-2 vaccine.

    – Bill H.

  53. Juggalo May 31, 2014 at 8:53 am #

    Dear Mr. Halford,

    the HSV529 vaccine is already in some trials in Maryland.
    Do you think the vaccine needs an adjuvant to work properly ?


  54. JohnC April 24, 2014 at 6:37 pm #

    Dr. Halford,

    there has been some kind of attenuated vaccine against HSV-1 & HSV-2 circulating in Russia. The vaccine called Витагерпавак (Vitagerpavac, Vitaherpavac) was invented in Saint Petersburg and is approved for use in Russia, where you can get it from medical personnel like dermatologists, etc. Supposedly a strong effectiveness against lesions recurrence is achieved in almost 2/3 of the treated patients.

    What do you think of this vaccine ?
    Would a comparative study against other vaccines, outside Russia, be realistic (at least in animal models) ?

  55. Bill Halford April 24, 2014 at 3:20 pm #

    Hi Glen,

    I think the GM-CSF is in Oncovex to aid with its primary therapeutic purpose……serving as an oncolytic virus that helps kill cancer cells. I think the way in which oncolytic viruses are currently being used (which is still in the exploratory phase; this is not a mainstream clinical treatment yet) is to (1) resect a cancer / tumor from the body and then (2) apply the oncolytic virus to the margins of the tumor bed to clean up (kill) and residual cancer cells that were left behind. The reason oncolytic viruses work is because they selectively replicates in cancer cells, but not in normal host cells; typically the difference is that cancer cells have lost their capacity to respond to interferon, and thus cannot mount an “interferon-induced antiviral state.” Thus, the primary purpose of Oncovex that is currently envisioned is to use the virus to help clean up (kill) residual cancer cells after a tumor resection, and presumably GM-CSF helps the oncolytic virus achieve this goal.

    With regard to a HSV-1 vaccine, I seriously doubt that GM-CSF would be required as a live HSV-1 virus would be more than adequate to elicit protective immunity against HSV-1. The issue is that we have never systematically tested a live-attenuated HSV-1 vaccine in a clinical trial. Hard to know how well an approach works when we (i.e., the FDA) are unwilling to test the approach.

    On this note, I find it a little bit odd that a live-attenuated HSV-1 virus like Oncovex is “safe enough” to put directly into patients’ brains after removing a tumor like a glioma (I am not making this up; this is published), but we are currently debating whether or not similarly attenuated live HSV-1 or HSV-2 viruses are safe enough to inject into someone’s buttocks as a vaccine. If I have to choose one shot or the other, I’ll take my live-attenuated HSV virus in the backside…..thank you very much. I am not the most safety-conscious / paranoid of the scientific lot, but the thought of a live HSV-1 mutant like Oncovex being put straight into my brain is a little scary. Of course, the reason this is being done is that the patients under study have run out of treatment options and have little time left until their gliomas prove fatal. Hence, even though a live HSV-1 mutant (Oncovex) in the brain is a bit scary, the alternative is a lot worse for sure. All I am saying is that if live HSV-1 mutants can be put straight in the brain, then it is kind of self-evident that a live-attenuated HSV-1 vaccine (less GM-CSF) would be very safe, and I predict would be highly effective in preventing all diseases caused by HSV-1.

    Finally, yes I think that the panel of 4 (or 5) gene knockouts in HSV-2 Immunovex rendered the virus “overattenuated.” If we ever get serious about testing live HSV-1 or live HSV-2 viruses as vaccines, we will certainly have to pay close attention to achieving the right balance between safety (avirulence) and vaccine efficacy (immunogenicity). However, this is a downstream question, as the larger debate right now is centered on the issue of whether or not we should even be testing live HSV viruses as vaccines. I think everyone here has heard my opinion on the matter. We will see what the powers-that-be decide to do. Maybe one day they too will grow weary of subunit vaccines that sound good on paper, but which routinely fail when advanced to clinical trials.

    – Bill H.

  56. Glen April 23, 2014 at 7:55 pm #

    Hi Dr. Halford,
    Thanks for your reply. My understanding is that the development of immunovex has been shelved for whatever reason. Presumably immunovex is faced with the same FDA issues that you have with regard to using a live attenuated vaccine. As someone who suffers daily with ghsv1, I guess my previous post was more related to the possibility of using oncovex against hsv1 rather than hsv2, especially given that it will potentially be available far sooner than other “bona fida” herpes vaccines. I was interested in your thoughts on the genes that have been inactivated in oncovex vs your own vaccine and whether you believe by knocking out these genes oncovex will be “too attenuated” to be an effective vaccine. I guess it would be no worse than acam-529 which is completely replication defective. Also I thought your previous comment regarding the elimination of the GM-CSF gene was interesting. Do you think that the addition of this gene is a bad thing? My understanding is that GM-CSF has been shown to be a promising vaccine adjuvant as well as being able to boost the number of DCs, which are obviously important antigen presenting cells. To my mind both of these factors might be advantageous to any vaccine strategy. Thanks again for your insight, it is much appreciated.

  57. Bill Halford April 23, 2014 at 6:46 pm #

    Dear Glen,

    The same company developed a live HSV-2 vaccine called “Immunovex” which went to a clinical trail in 2010 (http://www.herpes.org.uk/PRvaccine.pdf). Biovex was purchased by Amgen while the clinical trial was in progress, and so the data have not been published. So, in principle, you are correct that the idea of Oncovex can be adapted to a HSV-2 vaccine by (1) eliminating the extra GM-CSF gene and (2) switching to a similarly attenuated HSV-2 virus, which is precisely what “Immunovex” was.

    – Bill H.

  58. Bill Halford April 23, 2014 at 6:40 pm #

    Dear John C,

    There are a myriad of factors that contribute to host immune control of HSV-2 infection including (1) antibodies and (2) at least two major subsets of T-cells. I believe that it is an error in logic to believe that the detailed description of a new component of the host immune response to HSV-2 is a game changer in how we approach differentiating between “effective” versus “ineffective” HSV-2 vaccines. This population of CD8-alpha-alpha+ T-cells may be one contributing factor to the effectiveness of a HSV-2 vaccine (http://www.ncbi.nlm.nih.gov/pubmed/23657257), but my experience in the realm of herpes immunology would suggest to me that this is but one component in a cooperative network of B-cells and T-cells that create the final product of “robust vaccine-induced protection against genital herpes.”

    Yes, I would assume that all individuals have CD8-alpha-alpha+ T cells, and their presence in the skin in the case of genital herpes presumably reflects that this is primary location where HSV-2 replicates after exiting a nerve fiber (i.e., after a HSV-2 reactivation event).

    I would suggest that a more practical (feasible) metric of the potency / effectiveness of a HSV-2 vaccine would be to measure the total amount of IgG antibody present in the bloodstream that is directed against HSV-2’s total repertoire of antigens (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0065523). In general terms, the T- and B-cell responses to an effective viral vaccine will move in parallel, and these responses may very well include responses of CD8-alpha-alpha+ cells. However, when one considers the laboratory procedures required to measure IgG antibody versus T-cell responses to a viral vaccine, measurements of the antibody response are ~1,000 times faster and easier. Thus, for every viral vaccine in clinical use of which I am aware, the efficacy of vaccination is (1) typically measured in terms of the easily measure antibody response and (2) we generally assume that a proportional T-cell response will occur (e.g., see this publication…….http://www.ncbi.nlm.nih.gov/pubmed/18398296).

    Hope that answers your question,
    Bill H.

  59. Bill Halford April 23, 2014 at 5:53 pm #

    Dear Curing,

    I have been meaning to get back to you on this important question, but am fairly busy in the lab at the moment. There are certain times during vaccine-challenge studies where there is simply more to do than one person can get done……the past 3 days and the next 3 days are one of those time periods for me, but today is a recovery day.

    All I will say for the moment is that (1) your question effectively reduces to “How would a therapeutic HSV-2 vaccine work in reducing the symptoms of HSV-2 genital herpes?”, and (2) this is a very important question. I am long overdue for a blog post, and this is a sufficiently complex question that it merits a blog post.

    So, Curing, I will respond to your question in the next two weeks in the form of a new blog post with the primary goal of answering the question “How would an arm shot benefit the genital area for protective or therapeutic purpose?”

    – Bill H.

  60. Glen April 22, 2014 at 11:24 pm #

    Dear Dr. Halford,

    I was interested in hearing your opinion on the oncovex anti-cancer vaccine, which is based on a recombinant HSV-1 virus encoding the GM-CSF gene. I realise that this is marketed as a cancer therapeutic but do you think that this might have an off label use as a hsv 1 vaccine? Whether this therapeutic would be efficacious against hsv 2 is more of a stretch, but it seems to me that oncovex is akin to a live attenuated hsv 1 vaccine similar to what you are proposing to use for hsv 2 (albeit with different genes inactivated). Obviously oncovex is currently in phase III clinical trials and so is likely to hit the market far sooner than any other potential hsv vaccine candidates.

  61. JohnC April 22, 2014 at 4:42 am #

    Dr. Halford,

    there has been a recent discovery of the CD8αα+ immune cells, as a main factor contributing to suppression of herpes in the skin. Also the skin seems to be in the focus of interest and not the nerval tissue.
    Are all humans capable of generating these cells ?
    Would an effective vaccine in the future be measured by the response of these specialised T-cells ?

  62. Curing April 18, 2014 at 10:00 am #

    Dear Dr. Bill,

    let’s discuss the therapeutic effect of a future vaccine. So basically the patient gets a vaccine shot in his arm, just like all other vaccines are given. How does the human immune system respond next in the case of Acam-529 as an example ? Antibodies and T-Cells get generated.. would an arm shot be enough or yet better a shot in the behind area / under the belt ?
    How would an arm shot benefit the genital area for protective or therapeutic purpose ?

  63. Bill Halford April 14, 2014 at 9:29 am #

    Thanks JohnC. Good to know.

    – Bill H.

  64. JohnC April 14, 2014 at 9:04 am #

    Kickstarter platform sadly would not approve synthetic biology and similar campaigns.

  65. Bill Halford April 14, 2014 at 8:03 am #

    Hi Future Donor,

    A Kickstarter campaign sounds like a great idea, but I would prefer to wait until I have a firm commitment for a clinical venue in place before I start asking people to donate money and/or approaching venture capitalists.

    – Bill H.

  66. FutureDonor April 14, 2014 at 12:01 am #

    Hi Bill,
    How about creating a Kickstarter campaign to help fund human trials for your candidate vaccine? I bet you could raise a million dollars within a few weeks. I would be more than happy to donate a few thousand dollars.

  67. Bill Halford April 12, 2014 at 5:24 pm #

    Hi Yoshura,

    My latest take on the Genocea herpes vaccine trial is that the results being reported may be promising, but I cannot look at the reported “72% reduction” and conclude that is a slam dunk success. From where I sit, it just seems too early to know how this “72% reduction” compares to the effectiveness of valtrex or would compare to other therapeutic HSV-2 vaccine approaches.

    I think my opinion on the Genocea herpes vaccine trial will continue to evolve as the results of this trial are published. Until then, I will be watching and waiting along with everyone else.

    – Bill H.

  68. Bill Halford April 12, 2014 at 1:55 pm #

    Dear DB,

    You wrote “The the ImmunoVEX vaccine sounds like a like a very important piece of research, to validate your own work. Potential facts, that may be being overlooked in your pursuit. Considering all of the support and capability among your followers here, why dont you leverage this crowd to help you at least gather material, or investigate your own interest areas…..”

    I agree that the HSV-2-Immunovex clinical trial is a potentially important piece of science, but to the best of my knowledge the results of this clinical trial have not been published or thoroughly described in a public setting. Moreover, I am unaware of even a single animal-based study of the Immunovex vaccine, which differentiates (weakens) the approach relatively to a much better described HSV-2 vaccine candidate such as ACAM-529.

    While there may be a lot of support and capability amongst those individuals who choose to visit / follow this blog, it is unclear how to harness this energy and/or enthusiasm to tackle the multi-million dollar process by which a HSV-2 vaccine candidate would typically advance to a human clinical trial. I am not saying that it is impossible, but it is simply unclear to me how to translate / leverage the success of this blog (i.e., ~100,000 views since its inception in June 2013) into a human clinical trial of a new live-attenuated HSV-2 vaccine candidate like my lab’s HSV-2 0deltaNLS vaccine strain.

    I see that you are suggesting contacting the management and/or researchers at Amgen who are effectively now the owners of the HSV-2 Immunovex vaccine candidate. As I mentioned in my response to somebody else’s comment, I have not had a hugely positive response from companies that I have contacted directly to date. I don’t think this is a ding (negative reflection) on my science, but rather I think that people who work for companies tend to receive their marching orders from above, and tend to be unwilling to deviate off of what they have been instructed to do. Regarding the leadership of companies such as Amgen, typically the bottom line is that the success of the company really does not hinge upon the Immunovex vaccine, and in general HSV-2 vaccines tend to be a backburner issue for most companies. So, DB, I appreciate your suggestions and enthusiasm. However, I generally see that as a nation (or league of nations), we lack a rational mechanism to identify the most promising HSV-2 vaccine candidates and advance them to human clinical trials, and therein lies the core of the problem that separates my lab’s live HSV-2 vaccine candidate from human testing. In other words, it seems to not so much be an issue of “contacting the right person” as it seems to be an issue of “fixing a horribly dysfunctional system.” I have been to 3rd world countries where 50% of the population live in abject poverty that appear to be better governed than the governing bodies in the U.S. and Europe who are in charge of making our “vaccine development policy.”

    If my characterization of our current “system” seems unduly harsh, please consider my words against the backdrop of three facts and one inference:

    1. 50 million people have died of AIDS, tuberculosis, and malaria between 1990 and 2014 while vaccine-policy makers / companies have been pursuing subunit vaccines to prevent these diseases.
    2. By Christmas 2014, another 2 million people worldwide will have died of these exact same diseases in calendar year 2014.
    3. I saw no hint at the international vaccine meetings I attended in October 2013 and January 2014 that our “vaccine leaders” have any clue how to deal with HIV, tuberculosis, and malaria. What I say is a synopsis of what THEY said at these meetings; this is not me providing an overly harsh judgment of where things stand.
    4. Logically, this means that another 50 million people will die of AIDS, tuberculosis, and malaria between 2014 and 2040 while the search for safe subunit vaccines continues without ever considering the possibility that live-attenuated vaccines may be a more tractable solution to these serious human health problems.

    In my world, if this is the best plan that the governing bodies who set “vaccine development policy” can offer, then my conclusion is that these bodies have lost their way, and our current system is highly dysfunctional. Live-attenuated vaccines do pose a human health risk. However, we would have to come up with some really bad live vaccine designs to come anywhere remotely close to killing 2 million people per year with vaccines, which is currently what we are doing by virtue of not developing AIDS, TB, and malaria vaccines that offer a reasonable hope of success.

    Returning to your original question. I think advancing my lab’s live HSV-2 vaccine (which is uber-safe and highly effective) to a human clinical trial has less to do with contacting the “right people” and more to do with addressing the fact that our current “vaccine development system” is horribly dysfunctional.

    – Bill H.

  69. Bill Halford April 12, 2014 at 10:57 am #

    Hi Commentator,

    You wrote “I’m curious about these efforts for new anti-virals that remove viral DNA from latently infected cells: http://www.ncbi.nlm.nih.gov/pubmed/22718830. It always seemed most logical to me to simply remove the virus like we do with computers……”

    Many people are intrigued by such approaches but my experience suggests to me that this is an idea that sounds good on paper, but which is not practical. Unlike a computer virus that is bytes of code that can potentially be cleanly cut out, latent HSV genomes are DNA that is chemically very similar to our own chromosomes. So, in practice, you are talking about introducing a DNA-damaging agent in the body to remove a latent HSV infection. DNA-damaging agents, like sunlight and cigarette smoke, typically cause cancer. It has been argued that we can derive DNA-damaging agents / restriction-enzyme like approaches that are so highly selective that they would only damage HSV DNA. I note that even if such an approach was 99.99% selective for HSV DNA, that residual 0.01% non-selectivity would still be a signficant problem in terms of potential for cancer causation. So, at the end of the day, to remove HSV DNA from cells you have to be willing to accept the potential side-effect of cancer, and that is just a hard concept to sell to biologists.

    More to the point, if such an agent was actually devised, I am still unclear on how you would deliver it to all the HSV latently infected neurons. Are we proposing neurosurgery where we crack open people’s heads, lift the brain out enough to expose the trigeminal ganglia for HSV-1? Alternatively, for HSV-2, the virus can be parked in 2 to 6 ganglia lining the backbone, and so again we are talking about a pretty involved surgery if you want to directly deliver a HSV DNA-excising agent to the site of latent infection. An oral drug would be simpler, but we start to get into issues like (1) cost of drug, (2) survival in the stomach, (3) adsorption from the GI tract to the bloodstream, (4) delivery to the site of latent infection, and (5) potential off-target effects as a DNA-damaging agent spreads via the bloodstream to every organ in your body.

    Long story short…..there has never been a clinically viable drug in the history of medicine similar to what you propose (a molecular pair of scissors to cut out HSV DNA) and the same goes for the equally far-out and unproven proposal of DRACO. Importantly, getting “proof of principle” that these approaches might work in a cell culture dish only addresses about 0.1% of the problems that need to be addressed to obtain a drug that is useful in an intact animal / person. So, it is possible that these approaches might be applied to cure latent HSV infections, but I don’t think that most biologists in my field of study are particularly hopeful that these are realistic approaches.

    – Bill H.

  70. Bill Halford April 12, 2014 at 10:40 am #

    Hi Commentator,

    You wrote “Bill, a solution may be to bypass the NIH and go to a state or states…….”

    This is a really intriguing concept with which I am completely unfamiliar. Will take a look. I always assumed that the FDA’s federal guidelines superseded state laws, but maybe / apparently not. Will definitely look into this. Thanks for the suggestion.

    – Bill H.

  71. db April 10, 2014 at 8:33 am #


    The the ImmunoVEX vaccine sounds like a like a very important piece of research, to validate your own work. Potential facts, that may be being overlooked in your pursuit.

    Considering all of the support and capability among your followers here, why dont you leverage this crowd to help you at least gather material, or investigate your own interest areas.

    For example, we could be sending discovery requests, interviews to the biovex mgmt and researchers now at Amgen.

    Thank you for the dedication Bill.

  72. Yo shura April 10, 2014 at 1:07 am #

    Dr H.,
    What is your take on the latest results from Genocea herpes vaccine trail?


  73. Commentator April 10, 2014 at 12:47 am #

    I’m curious about these efforts for new anti-virals that remove viral DNA from latently infected cells: http://www.ncbi.nlm.nih.gov/pubmed/22718830

    It always seemed most logical to me to simply remove the virus like we do with computers. The viruses exists in cells, so you have to remove the viral code from the cells, that is what a real ant-viral should do so it can’t replicate anymore. I don’t understand enough to know if you could ever determine what code was a virus vs. good code in a human cell or figure out how to do that, but multiple people seem to be working on it.

    The alternative is the DRACO which induces apoptosis in all virally infected cells in the body. It works on all types. https://www.youtube.com/watch?v=TQhb1P3sMVs I’m unsure however if apopstosis of neurons would be safe. I don’t know what this would do the organ functionality of the CNS, root ganglia or other peripheral nervous system. I read it claimed that 11% of neurons could be infected in some part of the system, I wonder if you have any stats on what percent can be infected.

    These seem like two alternatives to the vaccine. I’m not sure they both work when a viruses is completely non replicating, but they seem to suggest they are.

  74. Commentator April 10, 2014 at 12:21 am #

    Bill, a solution may be to bypass the NIH and go to a state or states. You may offer patient advocacy organizations your research and suggest your research for state funding. A state bill could be drafted for a particular state to use a university of that state to conduct research. Further, perhaps multiple states could forward their funding to a single research program with inter-state cooperation. I recently saw Virginia did this to develop a new Lyme Disease test at George Mason University. The highly politisized and connected CDC and NIH had no interest in improving the test, but patient advocacy organizations in Virginia did and they got a bill sponsored to fund GMU.

  75. Bill Halford April 6, 2014 at 7:07 pm #

    Dear Curing,

    I am familiar with Akharameva, et al., 2011 (or thereabouts)…..I am pretty sure it was published in Journal of Virology. However, I am unsure if there is a question you are asking in this post.

    – Bill H.

  76. Bill Halford April 6, 2014 at 7:05 pm #

    Dear Michael,

    I am familiar with the fact that Immunovex was a live HSV-2 vaccine and entered a clinical trial in the UK in 2010. I am not familiar with what happened and why the silence, but multiple sources of information have suggested to me that whatever results were obtained were delayed in being published / reported because of the Amgen buyout of Biovex. I have no idea where the results of the Immunovex clinical trial stand, or what these investigators found.

    – Bill H.

  77. Bill Halford April 6, 2014 at 7:02 pm #

    Dear Help,

    I think the blood test results trump the swab results. If your HSV-2 blood tests keep coming back negative, and you don’t have any obvious symptoms, then I would suspect you are HSV-2 negative. However, I note that what you provide above is not exactly a complete medical history, so I would trust your doctor’s opinion more than my own given that I only have the words you provided (and not the facts) from which to draw a conclusion.

    – Bill H.

  78. Bill Halford April 6, 2014 at 7:00 pm #

    Dear Thewayiam,

    Lawyers (not scientists) write the forms that you are considering signing. What I can definitively tell you is that the HSV-2 ACAM-529 vaccine poses no real health risk that I can imagine, even in my wildest most far-out speculations about what could go wrong. So, I think that the safety of the HSV-2 ACAM-529 vaccine is a slam dunk.

    If you are a carrier of HSV-1 and get recurrent cold sores on your lips, it is possible that being vaccinated against HSV-2 could make your symptoms better, worse, or have no effect at all. While I have absolutely no concerns about the safety of the ACAM-529 vaccine, I am hesitant to suggest that it is likely that a HSV-2 vaccine could act as a therapeutic (curative) vaccine for HSV-1 cold sores. So, I can offer you no assurances that HSV-2 ACAM-529 will help with your cold sores. However, I note that vaccination with HSV-2 ACAM-529 should, at a minimum, leave you better protected against HSV-2 genital herpes should you encounter HSV-2 later in life. All of this is, of course, assuming that you are not in the placebo-arm of the trial.

    – Bill H.

  79. Thewayiam April 6, 2014 at 5:53 pm #

    Hi Dr. Bill,

    I’m considering joining the study for ACAM-529. I’m hsv-1 positive, on my lips, but hsv-2 negative. I was reading the waiver the Institute sent and got kind of scared by the paragraph that said “contact us if you develop blisters on your genitals or at the site of injection (which will be the arm)”. My main reason for joining the study is that hopefully I’ll get the vaccine, not the placebo, and will get some therapeutic benefit from it even though I could possibly get the antibodies for HSV-2 and will always test positive for hsv-1 and hsv-2 on an Igg test. If you were in my shoes, knowing what you know about the vaccine, do you think it makes sense for me to join the study? If I had hsv-2, I would be 100% in, but I’m afraid of coming out worst than I’m going in.

    Your input is appreciated.

    Thanks ahead

  80. Help March 30, 2014 at 8:45 pm #

    Dr. Bill, I have a question that maybe you can clear up for me. How can you have one positive swab, one negative swab and 2 negative blood test? Very confused if I have HSV2 or not. First blood test was one week before swab, second blood test 5 months later.

  81. Michael March 30, 2014 at 4:51 pm #


    Do you know what happened with the ImmunoVEX vaccine created by Biovex which entered Phase 1 trials in England in 2010. Biovex was bought by Amgen shortly thereafter and no new since. It appears as though this was a live attenuated vaccine. Are you familiar with this? The info states this vaccine uses 76 of 80 HSV2 proteins. Thanks!

  82. Bill Halford March 28, 2014 at 10:15 am #

    Hi Ivan,

    I have possible sponsors, but nothing more. As I have said before on this website, scientific opinion and human belief systems take time to change, and this is really where the primary focus of science lies……presenting people with the facts that effectively reduce to “If you want an effective HSV-2 vaccine and no more genital herpes, then a live HSV-2 vaccine is the logical path to pursue.” I have no doubt that scientists will come around, because scientists ultimately gravitate towards the truth……even if they initially don’t care for a new truth that they had previously overlooked.

    Once an adequate majority of scientists realize that we could stop the spread of HSV-2 genital herpes today with a live HSV-2 vaccine that actually works (unlike what we have been testing for the past 25 years), then a live HSV-2 vaccine will be forthcoming in short order. Until then, the debate goes on.

    The latest news I can report is that I have a new review forthcoming in the journal “Expert Review of Vaccines” that should be out in June 2014, and which is entitled “Antigenic breadth: a missing ingredient in HSV-2 subunit vaccines?” For those who are interested, this should make plain my argument why, at a minimum, we should at least start testing a highly safe live-attenuated HSV-2 vaccine in Phase I human clinical trials, and we should do this sooner rather than later.

    – Bill H.

  83. Ivan March 28, 2014 at 6:06 am #

    Dear Bill,

    How is you doing, did you find a sponsor for starting trials?

  84. Curing March 19, 2014 at 4:51 am #

    In this paper, Akhrameyeva et al. use tetracycline gene-switch technology (T-REx) and a dominant-negative mutant of HSV-1 replication binding protein UL9 (UL9-C535C) to construct a replication-defective HSV-1 recombinant (CJ83193) whose ICP0 gene (infected cell polypeptide 0) was replaced with mutant UL9-C535C controlled by a tetracycline operator (tetO) with an hCMV major immediate-early promoter.

    They took this recombinant HSV-1 went on to replace its essential UL9 with a HSV-1 glycoprotein D (gD) gene. And given its chimeric background, this secondary recombinant vaccine, dubbed CJ9-gD, when tested in mice, was able to elicit a robust and lasting specific humoral and T-cell response.

    They then revised this chimera to produce an HSV-2 recombinant (CJ9-gD2) to specifically address HSV-2. This vaccine, when tested in cultured cells was able to inhibit wild-type HSV-2 replication while remaining avirulent in mice when inoculated intracerebrally. It was able to induce a specific HSV-2 gD (gD2) neutralizing antibody response and T-cell response in immunized mice–additionally(!) having the capacity to protect mice after a post-immunization challenge and the establishment of latent viral DNA (decreased by ten-fold) compared to sham-vaccinated mice.

  85. David March 19, 2014 at 12:25 am #

    I’m curious, why did the Japanese not decide to investigate a live attenuated vaccine on other herpes viruses after the success of the chickenpox vaccine? One would figure that they’d be eager to experiment with an idea that has been successful in the past… And do you think your vaccine would be as good for HSV as the VZV vaccine is for chickenpox?

    Also if you ever accidently delete something, Ctrl-Z (or Command-Z on Mac) usually undoes the deletion job. Saves me all the time. Also, I’d just like to say thank you for your input and all of the work you’ve done over the years.


  86. Bill Halford March 17, 2014 at 10:20 pm #

    Hi Richard,

    Just got through typing over the last 30 minutes a very long and detailed response, and within a few keystrokes of finishing I managed to hit a stray button that wiped it all out; thus, you get the following, much shorter response.

    This is a great question and cuts to the heart of the issue. Logically, varicella-zoster virus (VZV) and herpes simplex virus (HSV) are the genetic equivalent of fraternal twins……not identical, but remarkably similar. So, if you can make a live-attenuated VZV vaccine that is safe and highly effective (in >50 million vaccine recipients), then you should absolutely be able to do the same in HSV-2. The VZV vaccine was not greeted with fanfare or immediately accepted, but rather, only grudgingly did American and European scientists (over 20 years of use in Japan) admit that their Japanese counterparts were correct that (1) a live VZV vaccine could be administered to millions of people safely and (2) a live VZV vaccine could be used to eradicate chickenpox, and eventually shingles. Specifically, Japanese scientists introduced the VZV Oka vaccine in Japan in 1974. Only after >10 years of being berated by their American and European colleagues for deliberately inoculating their population with a live herpesvirus did the Japanese scientists have enough data to proverbially reply, “Here’s the data; bite me.” In turn, Merck promptly purchased the intellectual property from the Japanese, and by the mid-1990s American children were starting to be injected with the exact same live VZV vaccine that was “too dangerous” 20 years earlier.

    A live HSV-2 vaccine could do the same for the human race, and spell the beginning of the end for genital herpes. Just a question of how long it takes the powers-that-be to, for the first time, to actually seriously consider using a live HSV-2 vaccine in humans.

    – Bill H.

  87. richard March 17, 2014 at 8:10 pm #

    What made it okay for a live attenuated chicken pox vaccine to make it to market? If a company was willing to back that product and bring it to market then why wouldn’t they back the same vaccine for hsv1 and 2?

  88. Dante March 17, 2014 at 8:04 am #

    Dear Dr Bill.

    What can you tell us about Vical vaccine called Vaxfectin there’s goind under phase 1 of trials.



  89. Curing March 14, 2014 at 6:58 am #

    Greetings Dr. Halford,

    A replication-defective version of a virus similar to your developed virus strain has been described by Natalie V. Akhrameyeva et. al., in the paper:
    Development of a Glycoprotein D-Expressing Dominant-Negative and Replication-Defective Herpes Simplex Virus 2 (HSV-2)

    The CJ2-gD2 virus represents a class of HSV-2 replication-defective recombinant viral vaccines in protection against HSV-2 genital infection and disease, which could also protect from HSV-1.

    Would this virus be possible to succeed to clinical trials, and if so, what would be the core difference between this virus vaccine, your virus vaccine and the ACAM-529 virus vaccine ?


  90. Bill Halford March 10, 2014 at 1:04 pm #


    I am a betting man and a student of history. As such, I tend to think that approaches that have worked in the past for other viral diseases (e.g., live-attenuated vaccines) are our greatest hope for a means of preventing HSV-2 genital herpes.

    Regarding what you are proposing, I think it is appropriate to say, “Never say never.” Is what you are proposing “possible?” Sure. Is what you are proposing “probable?” History and practical experience with antivirals would say that you are effectively talking about an approach to curing HSV-2 genital herpes that has as a great of a chance of succeeding as a lottery ticket has of making me a millionaire. Certainly possible, but not particularly probable.

    – Bill H.

  91. Vlad March 10, 2014 at 10:33 am #

    Thank you so much for your reply.

    I think the avenues of research to overcome the points you made are to deliver the RNA strands via an adeno-associated virus. With that delivery mechanism, it is my layman’s understanding, there is far less restriction on the molecular cutoff weight since the viral material insertion method bypasses the cytoplasmic membrane. With a long-enough strand, I would believe that the toxicity risk may decline because of its specificity?

    On cost, I think the idea behind the research is to generate the applicable strands but use PCR to mass-produce the required material for the AAV. The delivery protocol would actually insert the treated viruses at or very near the original point of infection, so that the treated viruses would also travel along the synaptic pathways just as the original virus did.

    Do these points in any way mitigate any of the concerns you raised? In particular, I am citing research and conversations had with Dr. Keith Jerome of the University of Washington, and based on his recent paper (February 4, 2014) : http://www.nature.com/mtna/journal/v3/n2/abs/mtna201375a.html

    Thank you,


  92. JohnB March 8, 2014 at 4:57 pm #

    Dr. Bill,

    Thanks for your reply! I hope that the trials underway for ACAM-529 go well and pave the way for more interest in live-attenuated vaccines for HSV-2. In theory, if ACAM-529 is more effective than sub-unit vaccines have been, then maybe that might begin to change the “mindset” about what might work best and what other different approaches are worth testing in humans – at least I would hope so!

    Is there any reason why a vaccine that proves to be effective in preventing HSV-2 wouldn’t also be likely to be “therapeutic” – since it seems to work that way for the shingles vaccine (though it isn’t 100% effective at preventing recurrence)? Isn’t the re-emergence of the virus from latency something that a vaccinated individual would theoretically have some degree of protection against? Is HSV-2 much different from VZV in the way it evades the immune system and goes from latent to active?

    Thank again for all of your work. If ACAM-529 shows interesting results, I hope the next step is funding and approving human trials of a live-attenuated vaccine.

    Thanks again,

  93. Bill Halford March 7, 2014 at 7:13 pm #

    Hi John,

    The antigenic breadth of the HSV-2 ACAM-529 vaccine is comparable to my lab’s live HSV-2 vaccine…..probably about 97 or 98% relative to wild-type HSV-2. Likewise, the effective VZV Oka vaccine retains >99% of the antigenic breadth of wild-type HSV-2.

    All of the HSV-2 vaccines tested previously in clinical trials contained 1 – 2% of HSV-2’s antigens; this is also true of (1) the Genocea GEN-003 vaccine; (2) the Agenus HerpV vaccine; and is likely true of (3) Ian Frazier’s HSV-2 vaccine candidate, but I have yet to see a detailed description of the Frazier / Corridon HSV-2 vaccine.

    Yes, herpesviruses are quite large, and are in general about 10-fold more genetically complex than the vast majority of human viral pathogens (e.g., influenza, HIV, poliovirus, HPV, Hep B virus, Hep C virus, Hep A virus, measles virus, etc., etc.). This is why I recently gave a talk at a vaccine meeting entitled “Herpes simplex virus 2 vaccines: sometimes size does matter.” The central point was that the cookie-cutter, one-size-fits-all approach to HSV-2 vaccine development is not a very smart idea, and lies at the root of why we still lack an effective HSV-2 vaccine.

    One day, the powers-that-be will catch up. Until then, I will keep pointing out (1) the fallacies in their logic and (2) the fact that HSV-2 genital herpes vaccines would be 100 times more likely to succeed in human clinical trials if we started testing HSV-2 vaccines that expressed 100 times more of HSV-2’s antigens (i.e., antigenic breadth = 99.3%).

    – Bill H.

  94. JohnB March 7, 2014 at 7:00 pm #

    Dear Dr. Bill,

    Thanks so much for your reply. I didn’t realize that the HPV virus was so small in comparison to HSV-2 and that the HPV sub-unit vaccine covers such breadth as a result. Has a vaccine for HSV with 20% or greater “breadth” ever been tested in people? What would be the approximate “breadth” of a vaccine like ACAM-529?

    If your live-attenuated vaccine is at 99%+ breadth, then no wonder it is highly effective in animals . . . I assume the effective live-attenuated VZV vaccine that we use also has very high breadth? I hope you will be given an opportunity to test your vaccine in human trials at some point!

    Thanks again for all of your work,

  95. Bill Halford March 7, 2014 at 4:11 pm #

    Hi Vlad,

    Honestly, this sounds pretty theoretical and impractical as an in vivo treatment that would be applied to living, breathing patients. Just because you can get a molecular methodology, such as you cite, in a cell culture dish does not mean that the approach would automatically work in real patients. Three of the big issues that would likely be a barrier to this being used to cure genital herpes are: (1) toxicity (i.e., things that alter the sequence of DNA are conventionally called mutagens, and mutagens in vivo (like sunlight an tobacco smoke) generally tend to cause cancer; (2) cost…..how much synthetic RNA does it take to treat a 90 kg human being?; and (3) delivery to the intended target in vivo……in this case a small population of neurons in the ganglia along the lower backbone that innervate the genital region.

    By-and-large, the molecular weight cutoff for most effective drugs is less than 5,000 Daltons and 200 – 500 Daltons is more typical. A single base of RNA has a molecular weight of 250 – 400 Daltons depending on which of the 4 bases we are discussing. Hence, the MW cutoff for a deliverable RNA molecule would likely be well below 20 bases, which (1) cuts into specificity of targeting and (2) raises further questions of how this thing will get across the cytoplasmic membrane and the nuclear membrane of a neuron that is latently infected with HSV.

    So, I return to my original point……highly theoretical, and probably not very practical as a human treatment for herpes.

    – Bill H.

  96. Vlad March 7, 2014 at 3:39 pm #

    Dr. Halford:

    I was wondering what your opinion is of the latest developments with CRISPR (clustered regularly interspaced short palindromic repeat) DNA loci and their ability to potentially act as a “silver bullet” to inactivate latent capsids in HSV-2 infected cells.

    I might be reading the technology incorrectly, but it appears that this relatively new technique can allow for the fabrication of RNA strands that can cut target DNA at specific sites and bind to the target or add repeated base pairs to also inactivate the virus if it is repaired.

    CRISPR techniques are being aggressively pursued to develop anti-viral treatments for HIV, but it would appear that the technique could also be used against any virus that has a latent-type capability. It might even be easier, I suppose, because it doesn’t appear that HSV-2 mutates as readily (or at all?) as HIV.

    Have you heard of any research that is being pursued using this technology to treat infected HSV-2 individuals?

    Thank you, and so much appreciate your dedication to the treatment of this psychologically devastating disease.

    Best regards

  97. Bill Halford March 7, 2014 at 12:35 am #

    Dear John,

    This is an excerpt from a HSV-2 vaccine review that I am writing, which at least partially addresses your question of why a subunit vaccine approach that worked for HPV (Gardasil) might not necessarily work for HSV-2.

    – Bill H.


    8. Antigenic breadth: a missing ingredient in HSV-2 subunit vaccines?
    Considerable effort has been invested into improving gD vaccines by modifying adjuvants or delivery systems. In contrast, little effort has been invested in addressing the more basic question, “Is it realistic to expect a vaccine based on 1% of HSV-2’s antigens to elicit 100% protection against genital herpes (Fig. 1A)?”
    Hepatitis B surface antigen (HBsAg) is the immunogen in the hepatitis B virus (HBV) subunit vaccine, and represents 12% of the antigenic breadth of HBV. Likewise, L1 is the capsid protein that self-assembles into virus-like particles in the human papillomavirus 16 (HPV-16) vaccine; the L1 protein represents 22% of the antigenic breadth of HPV-16. Therefore, a single protein represents a significant fraction of the antigenic breadth of these viruses because HBV and HPV-16 are tiny; their genomes are 3.2 and 7.9 kilobase-pairs in size, respectively.
    HSV-2’s genome, which is 50 times larger than HBV, is a 154 kilobase-pair DNA molecule, which encodes 39,107 amino acids of peptides distributed across 75 proteins. The Herpevac vaccine advanced by Glaxo Smith Kline was based upon 302 amino acids derived from gD, and represents 0.8% of HSV-2’s antigenic breadth (Fig. 1A).
    Given the complexity of the combined B- and T-cell response that naturally drives HSV-2 infection into a state of latency, I wrote an editorial in 2006 in which I made the argument that gD-based vaccines may lack the antigenic breadth necessary to serve as effective HSV-2 vaccines. The argument fell flat for lack of evidence to prove or refute the hypothesis. Fast forward seven years; extensive side-by-side testing of live HSV-2 vaccines versus gD vaccines has been completed. As predicted, a live HSV-2 ICP0- vaccine that encodes 99.3% of HSV-2’s proteins elicits greater protection. Below, I review the evidence that animals immunized with live HSV-2 vaccines are better protected against HSV-2 genital herpes than animals immunized with gD subunit vaccines.

    FYI, I define the term antigenic breadth as the percentage (%) of an infectious agent’s proteome that is present, or may be expressed, by a given vaccine candidate, and which may thus serve as the basis for immunogenic stimulation and clonal expansion of B- and T-cells (i.e., the foundation of vaccine-induced protection).

  98. JohnB March 6, 2014 at 6:24 pm #

    Hello Dr. Bill,

    I have a question for you about Ian Frazer’s vaccine work and it’s applicability to HSV vaccine development. It is my general understanding that his work on HSV-2 is derived from his pioneering efforts in developing the highly successful HPV vaccine that we have in use today (Gardasil) – that is to say that he is using a version of the same techniques, to develop a vaccine based on the protein expression signature of the virus itself, and by using these specific proteins to make the vaccine (not live or dead virus or viral particles). It worked with HPV obviously (using modified yeast to generate the proteins specific to the 4 targeted strains of HPV, and then using a concentrated shot of these proteins to stimulate immune response). What is the difference between HPV (which has an effective protein sub-unit vaccine) and HSV (in which protein sub-unit vaccines have to-date always been disappointing)?

    I have not seen much published data on the phase 1 trial he has going on the HSV vaccine, except that there was an update that announced that it was safe (no surprise) and that it produced immune response including antibodies and T-cells in non-HSV+ test subjects (a secondary goal of the study, but have we seen this before with other sub-unit vaccines that failed?). This alone is hard to interpret, since the data itself hasn’t been published – but the vaccine is also co-owned by a for-profit public company (Admedus, ASX:AHZ), so the “quiet” no details type of announcement doesn’t seem surprising – or really indicative of what’s going on either way. Is generating t-cell response in h- individuals something significant, if it is indeed verified?

    What is always hard in these cases is to separate the “stock promotion” from the true reasons to be optimistic/pessimistic about the vaccine/drug/whatever. AHZ owns 50.1% of Coridon (Frazier’s private company), so they have a lot of power to disseminate the message however they like – and an obvious interest in stock promotion in order to keep the stock trading up in order to finance further development and cash burn as needed (the stock is up over 350% in the last 12 months, but it’s a small-cap, obviously – and this is an area of the markets notorious for promotional PR and lack of transparency).

    The real question I have is “how good is the technology that created Gardasil?” It was ground-breaking, but does the approach have much of a chance to apply to other viruses (HSV, HIV, EBV, Hepatitis C, etc.), or was HPV particularly well-suited for that type of vaccine approach? Is there anything different in what Frazier is doing now than what others have already tried with HSV? He owns some patents, but it is not apparent to me that this makes much difference – companies have licensed his technology before (ie to make Cervarix) and it is not a secret . . . what are your thoughts on the technical aspects of applying Frazier’s “Gardasil style” vaccine development approach to other viruses? Is an HPV vaccine simply easier to design in certain ways that other potential virus vaccines are not? Is HPV just a more “simple” virus, more easily recognized by the immune system due to it’s signature proteins?

    Thanks so much for your great work! I agree wholeheartedly that the time to test a live-attenuated vaccine is ASAP . . . but I fear the market might be limited to therapeutic use due to fears of the words “live virus” and stigma among the populace . . . even the HPV vaccine was controversial, and it was just proteins (no live or dead virus at all). Perhaps we (people in the US) need better education about how science works, since too often it seems like the loudest and least informed voices end up leading the public debate (and influencing the powers that be).

    Thanks again,

  99. Norman March 5, 2014 at 5:25 am #

    Hello Dr. Bill,

    in a recent article
    there is mentioning about different strains of HSV. How much does genome sequencing help to combat the virus, and do we have to fear that more aggresive HSV strains could arise ?

  100. Dante March 4, 2014 at 6:57 pm #

    Hi dr Bill how are you ? About your vaccine when it was tested In mices did it prevent other mices from getting infected the vírus? And about medicine actions, did it relief the sinptoms on the mices? Or it cause some kind of “cure”?. Thanks again for having the patience to answer

  101. Bill Halford March 4, 2014 at 10:35 am #

    Curious Observer,

    Thanks for your observations. I will certainly take these into consideration, and do some more investigation.

    You said in your post “I must say, I certainly admire your passion, commitment and motivation to a seemingly impossible task.”

    I simply wanted to point out that in science, the task of bringing nature’s truth into the light of day is never impossible……it is simply slow, and so you must (1) push very hard on the glacier of popular opinion but (2) exercise patience in your expectations for how quickly the glacier will move in response.

    – Bill H.

  102. Bill Halford March 4, 2014 at 10:25 am #

    Hi Pam,

    My thoughts on ingesting food grade 35% Hydrogen peroxide to cure herpes are………close to zero. Seems like a pretty dumb idea. Why not just ingest battery acid and baking soda and see what happens. I would suggest we should keep the conversation focused on potential solutions that have a basis in reason, and try not to spend too much time or text on the proposals of witch doctors.

    – Bill H.

  103. Pam March 4, 2014 at 5:58 am #

    What are your thoughts on ingesting food grade 35% Hydrogen peroxide to cure herpes? Also when do you see a Herpes type 1 cure on the horizon? What about NB-001 cure for herpes type 1 do you think it’s going to work?

  104. Bill Halford March 3, 2014 at 8:29 pm #

    Dear Curing,

    I would suspect that 2 to 3 vaccinations with an effective HSV-2 viral vaccine, given every 4- to 6-weeks, should be sufficient to achieve a protective effect or (in theory) a therapeutic effect. Important to bear in mind that a preventative / protective effect of an effective HSV-2 vaccine is clearly an achievable goal. In contrast, a therapeutic effect, is a higher bar to clear and there is no historical precedent that informs us specifically whether or not a therapeutic HSV-2 vaccine is feasible.

    I am doubtful that ACAM-529 or any live HSV-2 vaccine would be as effective at preventing diseases caused by HSV-1. While there is some cross-protection, clearly a live HSV-1 vaccine offers a better opportunity to prevent diseases caused by HSV-1 than simply relying on the partial overlap of antigens between HSV-1 and HSV-2.

    Critical; harsh; truthful. In science, when people are chasing illusions or going down a dead end, one is faced with the choice of either being nice to their face and saying “good job,” while knowing in your heart of hearts that they are chasing phantoms, or you can do the more useful thing, which is harder to do, and be critical, harsh, and truthful and point out the fallacies in their logic that will be apparent to any critical scientist. I choose to do the latter because I am tired of seeing our limited resources to develop an effective HSV-2 vaccine squandered on approaches that should not work in theory, and have yet to succeed in practice.

    Bottom line: the potential to end the suffering of tens of millions of people who live with recurrent HSV-2 genital herpes is a lot more important to me than worrying about whether or not I offend the next scientist who proposes the next “promising HSV-2 glycoprotein subunit vaccine.”

    – Bill H.

  105. Curing March 3, 2014 at 3:35 pm #

    Dear Dr. Bill,

    thank you for your answer to the questions, which are critical and harsh, but before all truthful. Hope the scientific community realizes in time, that every safe and effective possibility to develop a vaccine should be exploited, for the benefit of humanity.

    Anyways, back to the topic on the ACAM-529 (Dr. Knipe’s vaccine), I have read a report, that says first tests showed protection/immune response against HSV-1 also in addition to HSV-2. This would mean we would have a general vaccine against both Herpes Simplex.

    Would the same cross-protection take place with your live-attenuated ICP0- vaccine ?
    How many booster shots would one human theoretically need, for good therapeutic and/or protective purposes ?

  106. Bill Halford March 3, 2014 at 11:10 am #

    Dear Curing,

    Vaccine-induced protection is typically mediated by a combination of antibodies and T-cells. In Iwasaki’s studies, she is using an artificial mouse system in which animals only have “HSV-specific T-cells” which are slow to leave the bloodstream and get to a site of HSV-2 genital challenge….if I remember the details of the paper correctly. Hence, she observes relatively poor immune control in animals that have lots of HSV-specific T-cells and a genital challenge with HSV-2, but she can overcome this by inserting chemokines in the vagina that artificially attract T-cells to the site of HSV-2 infection.

    In the real world this is impractical, and unnecessary. Vaccine-induced antibodies (molecules) are ~100-billion-fold smaller than vaccine-induced T-cells, and thus may leave the bloodstream and arrive at sites of HSV-2 infection much more rapidly….within hours not days. In nature, antibodies engaging their cognate HSV-2 antigens will activate the complement cascade, which generates pro-inflammatory signals which serve precisely the same function as the chemokines Iwasaki uses in her studies.

    So, I would not recommend trying to recapitulate Iwasaki’s results into a human HSV-2 vaccine by (1) only eliciting a HSV-specific T-cell response and then asking women to (2) douche everyday with a chemokine rinse to daily coat their vaginal vault with chemokines. Rather, I would say that the practical take-home message of Iwasaki’s results is that (1) HSV-specific T-cells are an important component of HSV-2 vaccines, but (2) another important is you have to provide a means to efficiently recruit T-cells to the “scene of the crime.” Nature learned this lesson hundreds of millions years before we did, and so she invented “antibodies” and the classical complement cascade to serve precisely this function.

    Take-home message: the most effective HSV-2 vaccines will elicit a balanced adaptive immune response that activates both (1) B-cells (the antibody producers) and (2) T-cells. My live HSV-2 vaccine does precisely this, and thus no chemokine douche is required.

    – Bill H.

    P.S. As I have made abundantly clear on this website, I think glycoprotein subunit vaccines are, in general, a very limited approach to vaccinate against HSV-2…period….end of sentence. Moreover, I note that scores of glycoprotein subunit vaccines against HIV, HSV-2, influenza, and seemingly every other viral pathogen have repeatedly failed over the past 25 years. I do not feel the need to explain why yet another iteration of HSV-2 glycoprotein subunit vaccine will most likely fail moving forward.

  107. Curing March 3, 2014 at 5:34 am #

    Dear Dr. Bill,

    could you shed some light and give your thoughts about another glycoprotein vaccine, in development by Vical ?

    also would be great to hear your opinion on the ‘pull’ concept of Dr. Iwasaki and if it could be incorporated into your existing vaccine research ?

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  109. Bill Halford February 27, 2014 at 8:27 am #

    Dear Curing,

    Great question. Yes, I have had fairly extensive conversations with people from Crucell and Sanofi Pasteur in person or in teleconferences, and I have had numerous, shorter conversations with individuals (i.e., lead investigators in vaccine development) from Merck, Glaxo Smith Kline and Novartis.

    The underlying issue is that a dogma / prevailing belief (developed in the 1980s) has come to completely dominate the thinking of vaccine companies and vaccine scientists. The dogma is that we should be able to cure every human infectious disease with safer vaccines that spun out from the recombinant DNA technology we developed in the 1970s. The basic formula goes (1) clone Immunodominant Gene X from Infectious Agent A; (2) overexpress “Immunodominant Antigen X” from Gene X; (3) immunize people with artificially produced “Immunodominant Antigen X” produced in Step 2; and reap the desired fruit…….(4) protect the human population against all diseases caused by Infectious Agent A.

    What the past 30 years of data (1985 – 2014) say is that the original idea of “safer vaccines” has not worked out as originally envisioned when we first became capable of DNA cloning……..such “safe, recombinant DNA (subunit)” vaccines have an overall success rate on the order of about 0.1%, which means that the overall failure rate is about 99.9%. This fact is quite apparent to scientists today, and is perhaps even more apparent to the clinicians who keep hearing that the next “promising” vaccine is entering clinical trials and is just “on the horizon.” However, these are empty promises. We know all too well in 2014 that only rarely is there a pot of gold at the end of the rainbow that is the next “promising subunit vaccine.” Unfortunately, from an investment point of view, such “promising” vaccines are still big business; I just spoke at a vaccine meeting in Washington DC four weeks ago, and it is apparent that the status quo from companies and the NIH continues in spite of what the data is overwhelmingly telling us. The fact is that the NIH and biomedical investors are all too willing to keep throwing money at the next “promising subunit vaccine” despite the abysmal track record of the approach (i.e., overall failure rate = 99.9%). This is why we still lack effective vaccines against HIV, tuberculosis, and malaria; these diseases have killed >50 million people in the last 20 years while we have been tinkering with “safe” subunit vaccines. Perhaps if vaccine companies were also responsible for digging the graves of people who died of the diseases that their “safe” (but ineffective) vaccines were supposed to prevent, then perhaps vaccine companies would be more open to considering the logical alternative that would reduce the time they spent digging graves. Live-attenuated variants of HIV, tuberculosis, and malaria have never been seriously investigated because vaccine companies spend all of their time chasing down the next “promising subunit vaccine.”

    So, getting back to your question, yes I have talked to a lot of companies. However, no, they are not interested in a live-attenuated HSV-2 vaccine because it does not fit neatly into their mental model of what a “good HSV-2 vaccine” should look like; namely, an (1) “Immunodominant Antigen X” protein subunit vaccine derived from HSV-2 or a (2) gene-therapy vector that expresses “Immunodominant Antigen X” of HSV-2.

    – Bill H.

  110. Curing February 27, 2014 at 7:36 am #

    Dear Dr. Bill,

    have you tried getting in contact with employees of pharmaceutical companies such as Merck & Co. or GlaxoSmithKline, which produce the VZV-vaccine, or companies affiliated with other live-attenuated vaccines ?

  111. Bill Halford February 26, 2014 at 8:46 pm #

    Dear Michael,

    Snake venom, arsenic, and falling from the Empire State Building all have the potential to stop one from ever having an outbreak of genital herpes again. However, I note that each of these “cures” may have some other side effects including a drastic reduction in one’s blood pressure and breathing rate. My general feedback is that snake venom and “snake oil” sound remarkably similar, and I don’t think either one is a viable cure for a HSV-2 infection or genital herpes.

    – Bill H.

  112. Michael February 26, 2014 at 7:40 pm #

    Hi Bill,

    I have been doing some research on snake venom. There seems to be consensus that most all animal venoms contain powerful antiviral properties. It seems like most of the research regarding venom’s antiviral properties is geared towards HIV. I have read your earlier comments describing HSV2 and for example, influenza, as apples and oranges, as far as the complexity/structure of the viruses goes. Does this same analogy apply to HSV2 and HIV? I would assume so because otherwise one would conclude there would be some crossover in terms of treatment, and there does not seem to be.
    My next question, is do you think the fact that a snake venom is a powerful neurotoxin, and seemingly has the ability to penetrate the nervous system, is a factor that might lead to greater efficacy in destroying the virus in its latent stage where it resides in the nerves?

    Of course I realize this is not your area of expertise, just looking for some general feedback.

  113. FatCat February 26, 2014 at 5:29 pm #

    Dr. Bill,

    Thanks for your informative reply. I can’t believe it has taken humanity so long to support development of a live-attenuated HSV-2 vaccine in people – not just the FDA, but around the world – it’s hard to understand, really.

    I understand the “fear” of giving people a “new” vaccine that might in very rare cases cause some type of symptoms (though it is like VZV or a lot of the other live-attenuated vaccines we are grateful to have and use, because they work).

    But treating people who already have exposure to the wild HSV virus seems like such a low hurdle (ie is the vaccine safe for these people, safer than the wild virus, and does it provide benefit, reducing symptoms or transmission).

    It’s just mind-boggling that human trials of the “most likely to work” vaccine approach have not been pursued for HSV like they have for other diseases. If the FDA can approve the Shingles vaccine, then the logic is sound that they “should” approve a good live-attenuated HSV-2 vaccine – both would have a similar use, to treat/prevent recurrences of symptomatic disease in people carrying latent H viruses.

    I also find it hard to believe that the CDC still doesn’t recommend including HSV-2 testing as part of standard STD screening (20-25% of adults in the US have HSV-2, and 80-90% of them don’t know they have it – we have the ability to test people, and doing so reduces transmission rates, but the CDC still thinks it’s better to keep people in the dark!).

    Knowledge is power and facts usually win out in the long run – so hopefully the tide will turn eventually. But I have also been surprised by how long people can maintain irrational behavior, so I just hope it doesn’t take forever to get there.

    This blog is great . . . maybe you can start a Kickstarter campaign to fund and produce a documentary? The story is compelling and if enough people understood the message, pressure for change might snowball – so often it’s visibility and public perception of issues that really drives policy (celebrity spokespeople help too of course, but one thing at a time!).

    Thanks again for all of your work.

  114. Bill Halford February 26, 2014 at 10:16 am #

    Hi Dante,

    My live-attenuated HSV-2 vaccine is currently in Phase 0 Clinical Trials……that is, it is not in a human clinical trial at the moment, nor have I currently identified a viable path forward to investigate its potential as a human vaccine to cure and/or prevent genital herpes.

    Regarding Dr. Knipe’s ACAM-529 vaccine, which is being advanced by Sanofi Pasteur……….this is currently in a Phase I clinical trial, whose primary goal will be to investigate how well it is tolerated (i.e., to evaluate its safety). If ACAM-529 keeps advancing through Phase 2 and 3 clinical trials (which it should), then perhaps we will start to get some idea of its effectiveness in 5 years. I am not privy to Sanofi Pasteur’s exact product development / clinical testing plans for the ACAM-529 vaccine, so all I can offer is this generality for now; I have no detailed knowledge of what trials are planned or their timing, and so I cannot offer a more concrete timeline.

    – Bill H.

  115. Bill Halford February 26, 2014 at 10:09 am #

    Dear FatCat,

    I have read this study, and I have to say that at first I was puzzled that it appeared in such an obscure pseudo-journal, but seemed to report what was effectively a cure for genital herpes. Even more puzzling, the (antigenic) relationship between HSV-2 and VZV is pretty weak, and thus it really makes no sense that a VZV vaccine should offer any relief to be people with genital herpes. In other words, the similarity between VZV and HSV-2 at the level of amino acid sequence of their viral proteins is so low, that you are correct that this does sound vaguely reminiscent of earlier efforts to cure HSV-2 genital herpes with all manner of unrelated vaccines (i.e., oral poliovirus; BCG; and the smallpox vaccine too).

    Now that I have defined all the things that I have found surprising about the article, here is what I find less surprising. I know at least 5 HSV-2 genital herpes sufferers who went out and got either the chickenpox vaccine or the shingles vaccine (i.e., two different doses of the same live VZV Oka vaccine strain). To a person, every one of them said they observed no changes in their symptoms of genital herpes. So, not sure how this group in France obtained their results, but I believe the important point is that other people who have tried the VZV vaccine in efforts to reduce their symptoms of genital herpes have not had much luck reproducing the results.

    Finally, I note that the smallpox vaccine, oral polio vaccine, and BCG / tuberculosis vaccine are all far more dangerous than the live-attenuated HSV-2 vaccine I have proposed, which is profoundly attenuated even in mice with severe combined immunodeficiency (i.e., boy-in-the-bubble mice). Perhaps it would make more sense to test a live vaccine to prevent HSV-2 genital herpes that is (1) safer than the ones I list above, and which is (2) antigenically related to HSV-2 (i.e., the key to how vaccines really work).

    – Bill H.

  116. Dante February 26, 2014 at 8:51 am #

    Hello Bill.

    About Dr David Knipe vaccine, which are the next steps in clinical trials and years if all goes ok so it Sanofi Pasteur could bring the vaccine to the market?

    And about the work of your laboratory in which phase it is ?

    Sorry for my lack of understading if you already anwser theses questions.
    thanks Doc.

  117. FatCat February 26, 2014 at 6:41 am #

    Hello Dr. Bill,

    Thank you for your valuable work in the service of humanity. Not that I matter much in the grand scheme of things, but of all of the various HSV1/2 vaccines (and hopes) that have risen and fallen over the years – I have to say that I like your live-attenuated work the best of everything, and something like ACAM-529 (non-replicating) would be second-best. If we can vaccinate against VZV, we ought to be able to do something similar that works for HSV, right? Keep up the great work, and hopefully lots of funding and support will come your way.

    I wanted to ask you about a French study that I saw claiming to have used VZV vaccine to “cure” people of HSV-1 and HSV-2 symptoms. I say “cure” because the study design reminded me of the smallpox studies of the ’50’s that seemed great at first (a cure for everyone!), but then failed miserably when controlling for the placebo effect.

    It seems well established that smallpox vaccine doesn’t actually do anything more than saline does to help people with HSV (never mind the risk of nasty side-effects that the smallpox vaccine entails). Is it likely that this is also the case with the VZV vaccine? I mean, it’s pretty safe, but why would it work against HSV in a placebo-controlled study? The risk in taking it is small, so no harm in trying it if people want to, but it seems like “no effect” is the most likely outcome. I just can’t understand why this study wasn’t double-blind and didn’t have it’s control group injected with saline to control for placebo effect – would it really have been that difficult or more expensive to set it up that way? It makes me wonder what these researchers were thinking . . . maybe they didn’t have enough funds for saline injections and controlled study parameters? Maybe they didn’t read the smallpox studies people did in the ’50’s?

    The study is linked below for reference:


    This blog is a great resource, by the way.

    And thanks again for your great work.

  118. Bill Halford February 25, 2014 at 1:51 pm #

    Dear Curing,

    It is getting harder to do experiments in monkeys, and personally I don’t see the point. If you are going to upgrade the species, I would suggest going to the relevant species….humans. As animal models of viral infection go, herpes simplex animal models are quite good, and I think offer a reasonable basis for rank ordering (prioritizing) which HSV-2 vaccines are likely to succeed in humans.

    All of my HSV-2 vaccine studies use attenuated variants of the HSV-2 virus.

    – Bill H

  119. Curing February 25, 2014 at 12:29 pm #

    Hello Dr. Bill,

    i just wanted to ask if it is permissible for you to do experimental studies on monkeys, and not just limit on guinea pigs and laboratory mice and would it bring something new ?
    Also, regarding your tested live-attenuated virus, do you use the human HSV-2 virus strain in an animal or some other animal-specific herpes virus strain ?

  120. Bill Halford February 25, 2014 at 1:23 am #

    Dear Staying Upbeat,

    Please allow me to clarify. There is currently no specific plan to test a HSV-2 ICP0- mutant vaccine in Hong Kong or anywhere else. I am simply exploring my options; that being the case, I cannot offer a meaningful timeline.

    No plans to start renting jet skis either. I was just trying to illustrate that an “overseas clinical trial” would simply involve the 96% of the world’s population who do not live in the United States, and because the world is such a big and diverse place, such a trial could take a lot of different forms.

    The original idea of the FDA was fine. However, I note that the original idea of the U.S. Congress was fine too. Likewise, the U.S. used to believe in the naive idea that a country should invest in their infrastructure [bridges, roads, etc]. I grew up in New Orleans, and always took comfort (in the 1980s) in the fact that the rest of the United States was more organized / more efficient / less of a banana republic. Today, it feels like the U.S. is tinkering with all the same lame ideas that made Louisiana so disorganized and 49th in the country in every good category…..no tax base, no rules, no centralized sense of purpose, and politicians who too often viewed their offices as a tool for influence peddling.

    What I generally observe is that the U.S. government is going the way of the Louisiana I grew up in………short on people with honesty, integrity, and the know-how to get things accomplished. It is this growing, systemic dysfunction in the U.S. that concerns me, much more than any specific fear of the FDA, and thus my efforts to develop a HSV-2 vaccine have expanded to include the entire world. No guarantees I will find anything better than we have here at home, but it cannot hurt to inquire.

    – Bill H.

  121. StayingUpbeat February 25, 2014 at 12:14 am #

    Dr. Halford,
    I noticed that you mentioned “I am actively working towards precisely that goal” in regard to a question about the potential for an overseas clinical trial and “hypothetically” that it would be acceptable if “I was offered the opportunity to conduct a HSV-2 vaccine trial co-sponsored by the University of Hong Kong” would I be off base in wondering if a clinical trial involving an ICP0 deletion mutant HSV-2 vaccine may be starting soon in Hong Kong?
    Lets say, hypothetically of course, that a trial was run in Hong Kong instead of the US. What does the clinical trial timeline look like there?
    For the record I would hit-up “Dr. Bill’s HSV-2 Vaccine and Jet Ski Rentals.” With the number of people waiting for something like this I bet I would get into a line that started somewhere in San Diego and if it didn’t end up working I could console myself with an afternoon on a jet ski. (obviously kidding; but it is unfortunate that something as revolutionary as your vaccine has a better chance overseas solely because of US red tape)

  122. Bill Halford February 17, 2014 at 4:12 pm #

    Hi Michael,

    I presumed your question was hypothetical in nature, and gave you a highly generalized (hypothetical) answer indicating that, in principle, I agree with your suggestion that a clinical trial outside of the FDA’s jurisdiction may be a viable means to get around the 800-pound gorilla that is the FDA.

    In practice, I am only 25% of the equation when it comes to ownership of the intellectual property (patent) of a live HSV-2 vaccine that is attenuated by virtue of introducing a mutation in the ICP0 gene of the virus; the other co-owners are (2) Dr. David Davido of the University of Kansas, (3) the University of Kansas, and (4) my home institution, Southern Illinois University. However, I am in essence the “point person” for this group of co-owners of the live HSV-2 vaccine concept, as I believe is evident from (A) this blog, (B) my publication record on HSV-2 vaccines, and (C) talks I have given at scientific meetings over the past 4 years.

    So, your question is, “Wouldn’t you anticipate resistance from the University (i.e., my patent co-owners)?” This is no longer a hypothetical question, but rather is a very specific question whose answer depends on the specifics of what type of “foreign clinical trial” was proposed. If, on one hand, I was offered the opportunity to conduct a HSV-2 vaccine trial co-sponsored by the University of Hong Kong in their main teaching hospital under the auspices of their infectious disease group, then I suspect that Dr. Davido and our home universities’ would fully support such a clinical trial; the outcome of such a trial could only serve to increase the value of this intellectual property and raise its visibility in the world of vaccine science. If, on the other hand, I was talking about setting up “Bill’s HSV-2 Vaccine and Jet Ski Rentals” on a beach in Tijuana, then I believe that Dr. Davido and both of our universities would offer significant resistance to this latter type of “foreign clinical trial.”

    Regardless of the specifics of what may (or may not) come to pass with a foreign HSV-2 vaccine trial, all I can say is that such a trial would be conducted after I gain the support of my patent co-owners, and thus there would be nothing to “resolve.” While I have not discussed such possibilities with my colleagues (patent co-owners) to date, this is only because a firm offer and/or concrete plan has not be laid on the table. If such an eventuality comes to pass, then Dr. Davido and our universities will discuss such an opportunity at that time.

    In a similar vein, a significant amount of work (which I oversimplified in my last, hypothetical response) would need to be done to establish (1) standardized-operating procedures, (2) quality-control measures, and (3) good manufacturing practices to produce a clinical grade vaccine that was ready to administer to patients. These are not insurmountable hurdles, but simply are technicalities that take time to work through. So, yes, there are a lot of specific details (including patent ownership) that would need to be considered to bring a live HSV-2 vaccine to a clinical trial either inside, or outside, of U.S. borders.

    – Bill H.

  123. Michael February 17, 2014 at 3:14 pm #

    Hi Bill,

    You Bio page indicate you and the university co-own the patent to your vaccine. Wouldn’t you anticipate resistance from the University and/or require the University’s permission for a foreign clinical trial? If so how do you presume to resolve this?

  124. Bill Halford February 16, 2014 at 10:56 am #

    Hi Michael,

    First off, sorry to hear about your diagnosis. Second, regarding startup costs if you remove the FDA and the army of attorneys that separate me from vaccinating people with a potential therapeutic HSV-2 vaccine, then the only costs left would be the scientific costs / production costs of doing what actually needs to be done…..vaccinating people rather than talking about the million-and-one hypotheticals that attorneys like to ponder.

    In another country with (1) their official blessing to proceed and (2) a disclaimer form that discloses the risk of being injected with a live-attenuated HSV-2 vaccine (like you sign when you go bungy jumping or skydiving, which I note are more dangerous activities), then the actual costs of doing the science and producing the product would be well below a million dollars; essentially the cost of buying the necessary equipment (e.g., laminar flow hoods, CO2 incubators, -80C freezers, ultracentrifuges and rotor), establishing an uber-clean laboratory space (~2000 square feet) to do the work and house the equipment, and the cost of paying 1 or more technicians to produce the product…..depending on demand. There would have to be numerous quality control steps, but my primary point is that when you get down to the nuts and bolts of producing a live viral vaccine, the basic technology is not exorbitantly complex.

    Most of what the FDA is selling people is protection from unscrupulous people and shoddily-made products. If you replace the FDA with a disclaimer form (which people do every day when they go skydiving, deep-sea fishing, jet-skiing, etc), then the cost of getting things rolling goes down by 30 to 50 million dollars. On this front, vaccine companies and the FDA collectively seem to believe that “a live HSV-2 vaccine” will never fly in the U.S. because of ill-defined “safety concerns.” This is sort of like the boogie man……everyone has heard of him for years / decades, but the evidence he exists is sketchy at best. The fact is that, per the science that I have published, my lab’s live HSV-2 vaccine is empirically safer than any of the live viral vaccines we currently inject into our children; my lab’s live HSV-2 vaccine is slow to cause disease in SCID mice, which are far more immunocompromised than people with end-stage AIDS. So, while wild-type HSV-2 causes a uniformly lethal infection within 8 days after inoculating immunocompetent mice or guinea pigs in the eyes (a harsh, but efficient route of inoculation), one of my lab’s live HSV-2 ICP0- mutant vaccine strains, HSV-2 0deltaRING virus, causes no visible disease in 80% of SCID mice over a 100-day-observation period following a similarly harsh / efficient inoculation of the left and right eyes with this HSV-2 ICP0- mutant virus. In contrast, the chickenpox vaccine (that we routinely administer to infants) produces chickenpox-like lesions in humanized SCID mice in less than 3 weeks (SCID = severe-combined-immunodeficiency = boy-in-the-bubble syndrome).

    The bottom line is that with a startup like I describe above, it would probably be possible to figure out in the first 50 persons tested whether or not a therapeutic HSV-2 vaccine (i.e., a functional cure) is even possible, and this should take far less than a year if the persons involved in such a trial had chronic (or nearly chronic) symptoms of HSV-2 genital herpes.

    If such a proof-of-principle approach proved that a live HSV-2 vaccine could work as a therapeutic vaccine anywhere outside the U.S. (i.e., where a live HSV-2 vaccine is not guilty until proven innocent via the FDA’s $50 million pay-to-play scheme), then a “fee for vaccination” approach on the order of $1,000 – $2,000 per person should be adequate to functionally cure people of HSV-2 genital herpes. It just depends how much it costs to pay doctors, scientists, attorneys, and administrative costs to make delivery of such a vaccine a sustainable business.

    Given how badly botched the HSV-2 vaccine development process has been to date, I think that an unconventional approach (outside the U.S.) is one option to figure out today (not 20 years from now) whether or not my lab’s live HSV-2 vaccine functions as a (1) preventative HSV-2 vaccine in discordant couples and as a (2) therapeutic HSV-2 vaccine in those who live with chronic symptoms of HSV-2 genital herpes. You find me a host country, I will bring my HSV-2 vaccine, and we can find out whether or not a therapeutic HSV-2 vaccine is do-able or not.

    – Bill H.

  125. Michael February 16, 2014 at 9:50 am #

    Hi Bill,

    I have sopped up all of the information I can handle in the two weeks since I have been diagnosed. I have a couple of questions.

    What are your thoughts on incorporating nanotechnology into treatment. I had read some scientific papers about using gold nanoparticles to deliver drugs more effectively to the body. I would assume you believe the use of colloidal gold/silver by itself is quack science, although I have no experience with it, and of course many of us are desperate and willing to try anything. A professor at the University of Massachusetts Amherst name Vincent Rotello was named in several of these articles. Although herpes by itself never came up as a topic, antiviral properties was a common theme.

    I have read your other comments regarding fundraising problems for your quest for a live vaccine. My question is this. Assuming I won the lottery tomorrow, how much money would you need to get the vaccine into production in another country free from FDA regulations? My instinct from yours and other’s comments is that it would be between $1-5 Million. I am not a wealthy man, although not impoverished either, but for a problem of this magnitude, this seems like not much money. I think somewhere like Costa Rica/Colombia/Thailand would be good locations. Also looking at a country like South Africa, where it is estimated 70-80% of women are infected with type 2….seems like an easy sell to the authorities. I think the sheer number of those infected, coupled a professional fundraising strategy, could yield these types of moneys. In short, what would it take to put you in a foreign lab for a year?

  126. Bill Halford February 15, 2014 at 1:37 pm #

    Hi Dante,

    The ACAM-529 vaccine strain and my lab’s live-attenuated HSV-2 0-NLS vaccine strain both offer the hope of a functional cure (i.e., a therapeutic vaccine). I have my doubts about all of the other approaches that you mention.

    – Bill H.

  127. Dante February 14, 2014 at 12:38 pm #

    Hello Bill!

    First of all congratulations on your web site and in your big effort to brig news to us about this heavy toe that Herp is.

    I’m male, i’m 23, i’m from brazil and recently discovered that I have genital herpes and I’m thinking my relationship life it’s over :-(.

    But life moves on.

    I have some question for you if u have the time to answer me.

    First, do you really think that at some point a cure will reach our hands? like the upcoming ACAM-529 vaccine trial that uses a modify version of the virus in it-self?

    Second, what u think about the work of Genocea? Seems like a good try?

    Third, I read recently a new discovery about a capacity of “making”, “reprograming”, steem cells in like 30 minutes.

    Seems a stupid question but this discovery about steem cells could imply in someway on how the virus could be beat it?

    Sorry for my english and thank’s again.
    God speed on your discovery’s Bill
    May u bless us all with a “end” to this burden.

  128. Paul Simpson February 11, 2014 at 12:12 am #

    Thanks for this Blog and for taking time to answer questions from all the folks suffering from this disease. It is indeed appreciated by all of us. :)

  129. Bill Halford February 10, 2014 at 11:50 pm #

    Dear Mike,

    I looked up the original article that describes pritelivir (http://www.nejm.org/doi/full/10.1056/NEJMoa1301150), and believe that it looks highly encouraging. This is similar in principle to AIC-316, and may simply be the same drug renamed…..have not had enough time to confirm this is the case, but I know that AIC-316 was a helicase-primase inhibitor and so is pritelivir.

    Based on the data, I believe that pritelivir will be a valuable addition to our arsenal of clinically useful anti-herpesviral drugs. When I have a moment to spare, I will read the paper cited above from cover-to-cover, and will update this reply if there is anything important I should add. Bottom line…..this looks and smells like the real deal, and should offer some relief for those whose symptoms are not completely controlled by valtrex.

    – Bill H.

  130. Mike February 10, 2014 at 11:41 pm #


    I read about a new drug Pritelivir that they say reduces shedding and outbreaks significantly. I know the FDA has it currently on hold but do you think it holds any promise?

  131. Bill Halford February 10, 2014 at 5:26 pm #

    Hi Remulus27,

    Yes, a therapeutic HSV-2 vaccine might work as a functional cure and stop the virus from reactivating itself all the time.

    – Bill H.

  132. Bill Halford February 6, 2014 at 10:07 pm #

    Hi Jim,

    I am actively working towards precisely that goal.

    – Bill H.

  133. Jim February 6, 2014 at 10:06 pm #

    Is it possible to test the vaccine overseas?

  134. Remulus27 February 2, 2014 at 6:04 am #

    Is there anyway to stop the virus from reactivate it self all the time? Do you see the possibillity to find a way to stop it at all?

  135. Bill Halford January 28, 2014 at 10:01 am #

    Dear Meja Mike,

    Unfortunately, the wheels of vaccine development turn slowly. The wheels continue to turn, but how long will it take for a therapeutic HSV-2 vaccine and/or a preventative HSV-2 vaccine to become clinically available? Great question. I wish I knew the answer, but I do not. I would estimate years to decades. Hopefully, the picture will become clearer with time, but right now it is unclear how far away we are from seeing an effective HSV-2 vaccine put into clinical usage.

    – Bill H.

  136. Meja Mike January 28, 2014 at 4:23 am #

    Dear Dr Bill,
    I got herpes from my boyfriend,

    And I feel too bad … I have big hope and faith in your research ..

    How soon though would this vaccine take to come out??

  137. Bill Halford January 3, 2014 at 9:26 am #

    Hi Chris,

    I am a scientist, which means that facts and data impress me far more than titles. You are entitled to your opinion, and have made your viewpoint clear, as have I. We will see what transpires moving forward.

    – Bill H.

  138. Bill Halford December 31, 2013 at 6:34 pm #

    Hi Greg,

    You are correct that valtrex would not interfere with the HSV-2 ACAM-529 vaccine. The basis of attenuation of the HSV-2 ACAM-529 vaccine is that although it is a “live HSV-2 virus,” it is disabled and unable to initiate viral DNA synthesis in the cells it infects. Likewise, valtrex and acyclovir work as antiviral drugs by inhibiting viral DNA synthesis in cells infected with wild-type HSV-2. Since ACAM-529 cannot replicate its viral DNA, there is nothing for valtrex or acyclovir to inhibit with regards to what ACAM-529 does in vaccine recipients. So, you are correct; anyone in enrolled in the ACAM-529 vaccine trial should be able to keep taking valtrex or acyclovir.

    Your second question was………..”One thing that remains unclear to me is why a vaccine of a damaged virus would elicit a greater immune system response than exposure to the original virus itself. If somebody is already infected with HSV-2, I’m not sure why giving them this vaccine would bolster their immune system even more.”

    I think there are two sub-issues to deal with here and those are:
    (1) the nature of the “damaging mutation” by which HSV-2 is attenuated in a live therapeutic HSV-2 vaccine like ACAM-529; and
    (2) why a live therapeutic HSV-2 vaccine might yield a reduction in genital herpes symptoms.

    Regarding the first issue of “how HSV-2 is damaged to yield a live HSV-2 vaccine,” I share your concern that HSV-2 ACAM-529 may be too damaged to function as long-lived HSV-2 vaccine. The act of viral replication is not a trivial component of how live viral vaccines work. Live, replication-competent viruses that are attenuated (slow or unable to cause disease) are the underlying basis for many successful viral vaccines used in clinical practice including vaccines that prevent the diseases of: 1. smallpox; 2. yellow fever; 3. polio; 4. mumps; 5. measles; 6. rubella; 7. chickenpox; 8. rotavirus; and 9. shingles.

    In contrast, the idea of a live, disabled HSV-2 vaccine like ACAM-529 (which cannot replicate) is an experiment within an experiment. That is, here is the list of prior viral vaccines that have succeeded in clinical practice which are based on live-disabled (non-replicating) viruses: ……
    That is, this is a new approach and there are no prior success stories that tell us the ACAM-529 vaccine will work. I hope it does, but it is a highly experimental approach. Certainly better than Herpevac, HerpV, or GEN-003, but at the end of the day there is no historical precedent that tells us that the ACAM-529 vaccine necessarily has to work.

    Regarding the second issue of “why a live therapeutic HSV-2 vaccine might yield a reduction in genital herpes symptoms,” I think there are two aspects to consider: (1) virus dose and (2) the nature of the resulting immune response. If one thinks about how the body perceives HSV-2 proteins as foreign, there is a huge difference between receiving a vaccine shot that contains 10 to 100 million infectious units of a live, therapeutic HSV-2 vaccine versus letting 1 to 10 copies of wild-type HSV-2 slowly reactivate and creep out of hiding. The natural event of HSV-2 reactivation is the product of natural selection, and what nature has selected for is a virus that is very good at creeping around the body and only slowly eliciting an immune response that kicks in 5 to 15 days after a recurrent herpes lesion has emerged. If you really think about how the adaptive immune response is “supposed to work,” there should be no such thing as recurrent herpes lesions…..and yet these do in fact occur. HSV-2’s capacity to reactivate and cause recurrent herpetic disease is undoubtedly linked to this virus’s capacity to evade recognition / suppression by the innate, humoral (antibody-mediated) and cell-mediated immune responses. However, I suspect that there is some other viral trickery at play that we don’t understand which may involve T-regulatory cells and suppression of a productive / protective immune response.

    Now, if we step back and think about a therapeutic HSV-2 vaccine, a shot delivered to the epithelium that contains 10 to 100 million infectious units of a live-attenuated HSV-2 vaccine is going to (1) express a truckload of HSV-2 protein and (2) drive a massive pro-inflammatory response, and it is possible that this type of therapeutic vaccine could cause the adaptive immune response to “no longer be tricked into non-responsiveness (anergy)” but could instead elicit a renewed / heightened / re-invigorated immune response that would be far more protective against genital herpes outbreaks than what was going on for years before when HSV-2 was allowed to creep around in back alleys and move around below the immune system’s radar.

    At least…..that is the idea behind a therapeutic HSV-2 vaccine. So, ACAM-529 might do the trick. If not, perhaps a real live-attenuated (replicating) HSV-2 vaccine would do the trick.

    – Bill H.

  139. Greg C. December 30, 2013 at 6:13 pm #


    Thank you for such a detailed answer. What you say makes a lot of sense and it’s a huge help for people just learning about this issue. I sympathize with your concerns about the regulatory barriers at FDA and I hope that a successful phase-1 trial will help calm FDA’s fears about unproven hypotheticals, regardless of its efficacy. I hope that in the future live virus trials will be scrutinized based more on the known risks and less on fear of new approaches.

    I also believe your answer gives me some insight into another question that was lingering in the back of my head: whether or not Valtrex would interfere with the ACAM-529 vaccine. My guess is that since that vaccine is replication-deficient and since Valtrex only inhibits viral replication, then Valtrex would have absolutely no effect on the vaccine. (so in the unlikely case that I am selected for the phase-1 trial in Bethesda, I might be able to continue medication).

    One thing that remains unclear to me is why a vaccine of a damaged virus would elicit a greater immune system response than exposure to the original virus itself. If somebody is already infected with HSV-2, I’m not sure why giving them this vaccine would bolster their immune system even more. I’ve tried to read up on this but immunology is really opaque for the uninitiated. Consider one paper by Knipe et al (http://jid.oxfordjournals.org/content/200/7/1088.full.pdf+html) which examined the effects of the vaccine in HSV-negative and HSV-1 seropositive guinea pigs. The conclusions suggested that “Thus, these studies indicate that [ACAM-529] represents an excellent candidate HSV-2 vaccine candidate for clinical trials in humans” but they didn’t (at least not in that particular paper) discuss the effects of the vaccine on HSV-2 seropositive guinea pigs, which would seem to be the obvious metric if somebody were designing a therapeutic vaccine.

  140. Bill Halford December 29, 2013 at 6:12 pm #

    Hi Jon,

    I must confess I don’t know the particulars, but I can tell you that there is no such thing as a topical treatment that can do anything but simply reduce the severity of outbreaks. In general, oral antiviral drugs that go systemic will be more effective than topical antiviral drugs.

    – Bill H.

  141. Greg C. December 27, 2013 at 1:37 pm #

    ” The safety question is the focus of Phase I, and is a no-brainer…..yes, it will be safe enough.”

    Hi Bill. What makes you so confident that this vaccine will be safe? I thought the main concern with this type (live-attenuated or replication-defective vaccine; not actually sure what is the distinction between those) was that it was seen as potentially less safe than a glycoprotein D subunit vaccine. I would love to have your insight.

  142. munkyhedJon December 26, 2013 at 1:37 am #


    What is your opinion regarding NanoBio’s topical treatment designed to disrupt the virus envelope in vitro for HS-1? I recall another article I read stating that scientists had found a way to activate the latent HS-1/2 virus completely and that this procedure, used in combination with the topical treatment could lead to a full activation and subsequent destruction of the virus in its host.
    NanoBio signed a partnership with GlaxoSmithKline a few years ago, but I haven’t seen any updates in recent years on either of these fronts.

    I’m glad to have discovered your work. A vaccine is certainly preferable to a topical, reactionary solution, but I’m interested to know your thoughts.



  143. Bill Halford December 23, 2013 at 12:03 pm #

    Hi Peter,

    Intelligence and accurate choices will win out in the end……they almost always do in science. However, I agree that it is unfortunate that it is taking so long. As I have said before, and I will now say again, it is time for leaders in the HSV-2 vaccine research field to own up to past mistakes, and talk to the NIH with a single, unified voice indicating that the U.S. approach to HSV-2 vaccine development needs to make a change in course. A live-attenuated HSV-2 vaccine is an obvious possibility, but has been largely ignored for the past 30 years due to (1) a few small errors in logic and (2) the misplaced belief that glycoprotein subunit vaccines would be sufficient to stop the spread of HSV-2 genital herpes. Errors in logics are the norm in science; we all make them. However, true scientists get up, dust themselves off, own up to these errors, and then make a change in course towards a scientific idea that will work.

    Hopefully, the NIH and leaders in the HSV-2 vaccine field are coming to the realization that what I say in this blog is the plain and simple truth, and that it is time to (1) quit wasting our human clinical trials on HSV-2 vaccines that are ridiculous long shots, and (2) start investing our human clinical trials in HSV-2 vaccines that make sense and will work. The HSV-2 ACAM-529 vaccine trial is a step in the right direction. Hopefully, this is a sign of things to come.

    – Bill H.

  144. Peter December 23, 2013 at 12:43 am #

    What a terrible tragedy that this can’t be dealt with by intelligence rather than greed.

  145. Marcos December 18, 2013 at 12:42 pm #

    Dear Bill,

    I am Brazilian from Salvador / Ba, was diagnosed with HSV-2 three years ago and since then I wait some medicine to prevent transmission of the virus and its recurrences. What makes me most sad and depressed is the possibility of infecting someone.

    I discovered your blog yesterday and is now in my favorites.

    Thank you for your commitment, effort and dedication. People like you, who devote their whole lives to research and studies, are the hope of a better and happier life for all mankind.

    As the distance does not allow me to volunteer my simple contribution will be sending messages to members of the FDA committee, for greater urgency in clinical trials in humans, using the various herpes vaccine available in the literature.


    Sorry for vocabulary (I used google translator).

    Again thank you very much.

  146. Bill Halford December 16, 2013 at 10:31 am #

    Hi Elie,

    Prior HSV-1 infection confers some cross-protection against HSV-2, but it is incomplete and not sufficient to prevent you from being infected with HSV-2. HSV-2 is a much more aggressive virus, that I believe has effectively evolved the ability to establish infections in people who have HSV-1…..an infection that most people acquire before they start grade-school.

    – Bill H.

  147. Elie December 16, 2013 at 1:41 am #

    Hey Bill sorry that I keep bombarding you with questions but here’s one last one if you don’t mind, Does HSV-1 provide immunity or protection against HSV-2? As in acquiring it in the same region (oral or genital) or even contrasting opposite regions. Thanks.

  148. Elie December 15, 2013 at 10:12 pm #

    Thank you for everything Bill, World needs more people like you.

  149. Bill Halford December 15, 2013 at 7:55 pm #

    Hi Anon,

    Animals (including humans) that are latently infected with HSV-1 are essentially impossible to infect with an exogenous HSV-1 virus at any anatomic site.

    This is because immunity is a systemic phenomenon; the mediators of immune protection live in the bloodstream, lymph nodes, spleen, and other lymphoid organs. So, yes, having HSV-1 orally confers considerable protection against exogenous HSV-1 infection of the mouth, exogenous HSV-1 infection of the eyes, exogenous HSV-1 infection of the nostrils, or exogenous HSV-1 infection of the genitals.

    – Bill H.

  150. Bill Halford December 15, 2013 at 7:50 pm #

    Hi Brittany,

    If Coridon does not release any specific data and a detailed description of what their HSV-2 vaccine is, then I am as in the dark as you. Common sense tells me that if Coridon’s vaccine was all that, then they would be more than happy to show the data that proved their case.

    – Bill H.

  151. brittany December 15, 2013 at 4:55 pm #

    Coridon should be available before Acam 529 and people are saying it is a cure. Bill, is Coridon really going to cure herpes? media reports have quoted Ian Frazer as calling it a cure but they won’t answer emails to confirm it. Is it a cure? Why won’t they answer?

  152. anon December 15, 2013 at 3:16 pm #

    Hi Bill,

    Thank you once again for all of your insight.

    I think Elie asked, and I am curious too, if you could shed some light on the notion that having HSV-1 orally is protective of acquiring HSV-1 genitally.


  153. Bill Halford December 15, 2013 at 9:01 am #

    Hi RFQ,

    Yes, I concur. Oral or genital does not matter……HSV-1 and HSV-2 infections at any anatomic site on the body can produce symptomatic or asymptomatic infections.

    – Bill H.

  154. Bill Halford December 15, 2013 at 8:58 am #


    Your HSV-1 is almost certainly just oral, and your lower body rash is probably eczema or some other skin condition. Trust your doctors more than me on the cause of your skin rash. I would classify someone as a high reactivator who has outbreaks once every 3 months, or more frequently. Clearly, this is not you.

    – Bill H

  155. Elie December 15, 2013 at 2:48 am #

    I cannot thank you enough for the thorough response and many signs of relief you have given me.

    If I may add in my entire life (23 now) and believe I have received it from my parents who are also positive. Does 2 outbreaks of cold scores in 23 years classify me as a high reactivator? And in relation to having oral HSV-1 is it possible I have genital HSV-1 but am asymptomatic (never had genital symptoms Doctor believes this persistent lower body rash I have is only Dermatitis) as the blood test simply claimed HSV-1 positive whilst facial sores were visible which leaves me wondering if I may have genital HSV-1 and if you could clarify rumours of oral HSV-1 antibodies providing some immunity to other types of HSV.

  156. RFQ December 15, 2013 at 1:18 am #

    “The spectrum of outcomes of genital HSV-1 or HSV-2 infections is incredibly wide……from a completely asymptomatic primary infection that slips under someone’s radar for life to a never-ending series of herpes outbreaks that just come one after the other.”

    Can’t we say the same thing about oral HSV-1? I think the spectrum is pretty similar. People definitely get never-ending outbreaks from oral HSV-1, but most people don’t and are blissfully unaware they have it. Same goes with HSV-2. The spectrum of outcomes for genital HSV-1 is even narrower and less worrisome.

  157. Bill Halford December 14, 2013 at 2:07 pm #

    Hi Elie,

    My general rule of thumb with a completely asymptomatic, oral HSV-1 infection would be not to worry about it. If you had symptoms with any regularity, and could predict when you might be shedding infectious virus, then by all means take some precautions when there is a discernible risk. But if you are at the other end of the spectrum, and never have coldsores, what sort of precautions would you take and how often would you take them? If you take this logic to its ultimate conclusion, you would have to quarantine yourself away and never contact another human being again. I don’t see changing your social behavior over the theoretical risk of transmitting oral HSV-1 to another person.

    The simple reality is that I have given influenza virus and lots of other infectious agents to friends and family members, and likewise have received the same in return. We simply don’t live in a sterile world, and I think that the germaphobe approach to infectious disease is well-meaning but misguided. I would put your concern about an asymptomatic oral HSV-1 infection into this category, as it is nothing more than a theoretical possibility for which you have no hard proof. Yes, you could occasionally shed low levels of infectious HSV-1. Statistically, I bet it is a 100 times more likely that people who get visible cold sores once or more per year serve as the major source of transmission for HSV-1 to other people. These “high reactivators” also have asymptomatic periods, and it is far more likely in their case that they may be shedding HSV-1 during their asymptomatic periods, so it is more relevant for “high HSV-1 reactivators” to be cognizant of prodrome symptoms and avoid oral sex or giving someone a kiss when they have any inkling that they are at real risk for shedding HSV-1.

    However, I don’t think that it is realistic to suggest that people who are completely asymptomatically infected with HSV-1 should modify their behavior; about half of the human race is asymptomatically infected with HSV-1, it is just that most of them are blissfully unaware. Elie, I don’t think that you should be penalized for having knowledge that you are asymptomatically infected with HSV-1.

    Finally, I believe that genital HSV-1 or HSV-2 infections belong in a whole different category. The risk of transmitting HSV-1 or HSV-2 to a love interest during sexual intercourse is a life-altering event, and so full disclosure is the key. The spectrum of outcomes of genital HSV-1 or HSV-2 infections is incredibly wide……from a completely asymptomatic primary infection that slips under someone’s radar for life to a never-ending series of herpes outbreaks that just come one after the other. Because of this wide spectrum of clinical disease, I am not a fan of “one size fits all” advice in telling people how to deal with a genital herpes diagnosis, particularly when it comes to entering into discordant relationships. The only catch-all advice I can offer is that full disclosure is pivotal, so that both halves of a prospective couple can enter into the relationship with full knowledge that (1) there are some risks but (2) these risks may be managed and ARE MANAGED by hundreds of thousands (millions?) of discordant couples around the world.

    That was the long answer. The short answer is that, Elie, in your case…..I would not sweat your status as an asymptomatic carrier of oral HSV-1, which you share with about 3 billion other people.

    – Bill H.

  158. Elie December 14, 2013 at 3:30 am #

    Hey Dr Halford, I’ve been reader for a few months now and after extinguishing all avenues I thought maybe you could shed some light compared to mixed advice I’ve been receiving. Being HSV 1 positive with no symptoms whatsover, cold sore healed ago. I’m still contagious? Asymptomatic shedding still occurs? And pretty much my culture greets guests with kisses on the cheek. Thanks.

  159. Bill Halford December 11, 2013 at 9:58 am #

    Hi Matt,

    This is what the Viradux website claims…..

    “Viradux-AU is a suspended solution containing both herbal extracts and a natural transdermal delivery medium. The manufacturing process involves an electrolytic treatment using rare earth minerals that allows the medium to be easily incorporated deep inside the cells of the spinal ganglia.”

    Viradux AU is about as real as Santa Claus.

    I would suggest that acyclovir or valtrex are better alternatives for managing the symptoms of herpes.

    – Bill H.

  160. Matt December 11, 2013 at 5:17 am #

    Hi Dr Halford, I recently purchased this product http://www.viradux.com in desparation after recently contracting HSV-2 from a trusted partner. I was wondering if you could take a look and shed some light on if there is any scientific truth whatsoever to their product. I believe I’ve been duped but like I said I was desperate. Thanks very much for your time.

  161. Bill Halford December 3, 2013 at 10:30 pm #

    Hi Anna,

    Thank you. The fact that I could write something that restores anyone’s faith in humanity (even a tiny bit) is reassuring. I have spent much of the past 12 years writing to NIH study sections trying to explain why my research is relevant, and explain why funding for my lab’s research would be a good investment of U.S. taxpayer money. The dominant responses that I have gotten back from NIH reviewers to date tend to fall in one of three categories, and these are:

    1) Grant triaged, and I don’t need to justify why I made this decision.
    2) Grant triaged because I don’t know who you are, and I certainly know that people more important than you are already doing similar research.
    3) Grant triaged because we already have many HSV-2 vaccine candidates, and we certainly don’t need a live-attenuated HSV-2 vaccine.

    A NIH grant takes me a month to write. Getting grant after grant back from NIH reviewers without a full panel review (i.e., this is what “triaged” means) is a bit soul-crushing, particularly when I know (1) the world needs a HSV-2 vaccine that works and (2) the NIH should be willing to support research that improves our odds of getting there.

    After being beaten down by the NIH’s dysfunctional funding system for so many years, it is nice to hear that the HSV-2 vaccine research led me to create a blog that is of some value to the people who really count……people dealing with HSV-2 infection and its many ramifications.

    – Bill H.

  162. StayingUpbeat November 30, 2013 at 5:00 pm #

    Dr. Halford,
    I wanted to let you know how popular your blog has become both in post conversations and in providing rational backup to discourse when people discuss ongoing research. I hope I’m not becoming a broken record but thank you again for your time and effort.

    Happy thanksgiving!

  163. Anna November 30, 2013 at 4:33 pm #

    Dr Halford, after searching for answers to this dreaded HSV 2 you are the first person who makes sense in the medical information you provide which is informative and honest. Awaiting a miracle after discovering my status knowing that I have had only two sexual partners in all of my 44 years and have resigned myself to celibacy rather than attempt a relationship.

  164. Anna November 30, 2013 at 4:17 pm #

    Best response from the medical world I have read. Restores a tiny bit of my faith in humanity.

  165. Bill Halford November 26, 2013 at 8:28 pm #

    Hi Sweet 7,

    There might be something worthwhile to consider in this study, but I have not had a chance to fully read this paper from cover to cover. I just wanted to point out the (1) rationale behind including a positive control in a HSV-2 vaccine-challenge study, and (2) point out that the methods and data in this paper suggest that the positive control treatment (HSV-2 tk- mutant) may not have been delivered in a manner that allowed the live HSV-2 vaccine to elicit the full protection against HSV-2 that it could have.

    Thanks for the question. Will read this paper for real as soon as I have time.

    – Bill H.

  166. Sweet7 November 26, 2013 at 7:14 pm #

    Thank you Bill. I thought the three variables were confusing which is why I only skimmed it myself. Then after reading that sentence stating that the live attenuated vaccine was superior, my mind was blown. Am I making the correct assumption that it means that the attenuated vaccine used in the control was superior to the other vaccines in this study? If that is the case and the animals were only dosed once, then I would like to ask these researchers why they are even bothering.

  167. Bill Halford November 26, 2013 at 6:43 pm #

    Hi Sweet 7,

    I think the reason that the investigators used a positive control is in part due to an argument that I made in my 2011 and 2013 studies, that HSV-2 vaccine-challenge studies should include both a (1) negative control and a (2) positive control. All HSV-2 vaccine studies have always included a negative control of animals that have not been immunized, or who were injected with an irrelevant liquid like saline. However, positive controls have been notably absent in HSV-2 vaccine-challenge studies prior to 2011, and this is a major beef of mine that I discuss in my blog post on “Proper Vetting of HSV-2 Vaccines.”

    The idea of a positive control in this setting is that there should be one group of animals that are as maximally protected / immunized against HSV-2 as is humanly possible, and which serve to establish a benchmark for what “100% protection against HSV-2 genital herpes” should look like in the animal model. Then, and only then, can you ask, “What percentage of possible protection is elicited by my HSV-2 vaccine?”

    Kudos to these investigators for including a positive control in their animal experiments. That said, let me suggest some ways they could improve upon their positive control.

    All of the groups of mice that receive the vaccines of interest to the investigators are immunized three times on Days 0, 14, and 28. In contrast, the animals that receive the positive control are given a single, low-ish dose of the live HSV-2 tk-mutant virus (+ control) on a single occasion on Day 0 by a completely different route of administration. I would (1) ramp up the dose of the live HSV-2 tk-mutant and (2) I would administer three doses of the live HSV-2 tk-mutant virus at the same times and injection sites as the vaccines of interest. This way you are just comparing one variable…..the immunogen, rather than comparing 3 variables (immunogen, number of immunizations, and immunization site).

    Long story short, I think these investigators have deliberately low-balled the positive control immunization and this accounts for the staggering amount of variance in the quality of protection elicited by the “positive control” HSV-2 tk- mutant virus. For example, in Figure 2, if you look at the amount of HSV-2 DNA copy number detected in vaginal swabs on Days 1, 3, and 5, the error bars span a 10,000-fold range (4 full logs). That is like me saying, the population of New Orleans is somewhere between 10,000 and 100,000,0000 (i.e., 1 million people give or take 2 logs).

    I remember receiving a document via e-mail in graduate school entitled “Scientific Phrases and What They Mean.” The one that is relevant to my comments above is:

    Bottom line: I am glad that investigators in the HSV-2 vaccine world are starting to include positive controls, but I think another key step is to immunize with a high enough dose of the HSV-2 tk-mutant to see the full effect of a live HSV-2 vaccine. Based on the Materials and Methods and the data presented in Figures 2 and 6, I believe the investigators deliberately tried to minimize the protection elicited by the “+ control” in order to make the gD vaccines of interest look better. I also note that it is odd that the positive control is absent from Figures 3 and 4. If you include a positive control in a study, you typically include it in all analyses. Will need to read the paper more carefully…..perhaps there is a rationale there that I am failing to grasp because I have only skimmed this paper so far.

    – Bill H.

  168. Bill Halford November 26, 2013 at 6:13 pm #

    Hi N.S.,

    Regarding the waiver………..I wish it was that easy!! Sorry to hear about your situation. If I figure out how to get a clinical trial of my lab’s HSV-2 vaccine going, I will be certain to post that information here.

    – Bill H.

  169. Sweet7 November 26, 2013 at 2:00 pm #

    In the link above regarding Coridon’s vaccine, A Novel DNA Vaccine Technology Conveying Protection against a Lethal Herpes Simplex Viral Challenge in Mice, in section Figure 1. Survival, following HSV-2 challenge, of mice immunized with codon-optimized polynucleotides encoding antigen and ubiquitinated antigen.
    it is stated that a mouse thymidine kinase-deficient live HSV-2 strain was used as a control in 5 mice. Then the last sentence stated “The positive control live attenuated HSV-2 vaccine provided superior vaginal load protection at both inoculum levels”.
    I’m not sure if I am understanding this correctly but this made me question why they used a live attenuated virus as a control? Is it because they already know that a live attenuated virus had a chance at being superior?

  170. N S. November 26, 2013 at 1:11 pm #

    Hello Bill. Thank you entirely. You’ve been my savings grace in regards to true hope and good information about a cure for this. This last spring, I contracted HSV-2, not only on my genitals but also on my face, at the same time. I was visiting a friend in new york, and had been bitten by a tick at the same time. I was developing a red ring around my tick bite when i contracted the HSV-2. Having taking some anti-biotic for the potential lymes disease, i think i may have weakened my immune system, as i have read in staticstics that is is highly unlikely to show symptoms in both mouth and genitals.
    Anyways, since then i have remain hopeful about new possibilities for vaccines. I can’t let this disease dominate my life. I recently had some blisters on my thumb and i hope to high heavens that it isn’t herpetic withlow, but it looks a lot like it. This new disease doesn’t cause me much pain but a lot of psychological distress.

    I was curious if there was a waver one could sign, something to allow me to test your vaccine without you being liable.
    I would do anything.

  171. Bill Halford November 24, 2013 at 8:12 pm #

    Dear Dean,

    Yes, I will be happy to decipher. This is more of the same nonsense that I keep talking about.

    This is another study where the sole HSV-2 antigen that forms the basis for the vaccine is HSV-2’s glycoprotein D protein. Just to clarify, let me list of a few of HSV-2’s other protein antigens / immunogens that appear to be important in my studies, and these are:

    HSV-2’s ICP8 protein,
    HSV-2’s ICP10 protein,
    HSV-2’s VP5 protein,
    HSV-2’s VP1-2 protein,
    HSV-2’s glycoprotein B,
    HSV-2’s glycoprotein H,
    HSV-2’s UL40 protein,
    HSV-2’s UL48 protein,
    HSV-2’s UL21 protein,
    HSV-2’s UL47 protein,
    HSV-2’s DNA polymerase,
    HSV-2’s UL42 protein
    HSV-2’s glycoprotein E,
    HSV-2’s glycoprotein C,
    HSV-2’s UL49 protein,
    HSV-2’s UL38 protein,
    ……oh and HSV-2’s glycoprotein D.

    The normal, full-blown protective immune response against HSV-2 involves lymphocyte engagement of 20 to 30 viral proteins. Probably at least 10 HSV-2 proteins need to be presented to the immune system if a vaccine recipient is going to have any hope of better recognizing HSV-2 in the future, and thus having real protection against HSV-2 genital herpes.

    In contrast, papers like this one are essentially claiming / promising that a vaccine based on HSV-2’s glycoprotein D plus some additional bling (ubiquitination of glycoprotein D) will yield an effective HSV-2 vaccine. However, I note that HSV-2 glycoprotein subunit vaccines failed to elicit meaningful protection in human clinical trials in the 1980s, 1990s, 2000s, and again in 2012. I am not hopeful that a HSV-2 glycoprotein D vaccine can be re-packaged or revamped, such that suddenly a strategy that has been failing in clinical trials for 25 years will yield a different result in the future.

    The underlying issue is that glycoprotein D is just 1 of 75 HSV-2 proteins, and this is simply not enough to teach the immune system “what HSV-2 looks like” and/or how to find and destroy HSV-2 when it enters a vaccine recipient’s body. The simple reality is that a large number of HSV-2’s other 74 proteins appear to contribute to HSV-2 vaccine efficacy, and unfortunately they are missing from the glycoprotein D + ubiquitination pathway modifications that are the focus of the study you cite.

    Bottom line: HSV-2 is not a big ball of glycoprotein D antigen……it is a complex life form that encodes 75 proteins, many of which are far more important to human immune recognition of sites of HSV-2 infection than glycoprotein D. I think that an effective HSV-2 vaccine will need to be based on many other HSV-2 proteins in addition to glycoprotein D.

    – Bill H.

    P.S. I do not address the ubiquitination issue head-on because I view this as a novelty that the authors invoked to get their paper published, but not anything that is really germane to how HSV-2 vaccines work.

  172. Dean November 23, 2013 at 2:26 pm #

    Hello Dr. Halford,

    I believe this is the study you are looking for and the current Phase 1 trial is based on:


    As far as I understand, the new technology is based on ubiquitin-mediated protein degradation processes in human cells – discovery that won the Nobel Prize in Chemistry in 2004. :


    I am not very familiar with either the vaccine technology or the process of ubiquitination but I am sure that there would be a lot of people on this blog that would appreciate your opinion on the subject matter. I would certainly be one of them and I would really appreciate if somebody could translate this information in a more accessible and understandable way to the general public.

    Thank you for your efforts,

    – Dean

  173. Bill Halford November 22, 2013 at 4:00 pm #

    Dear Thankyou,

    My time is pretty limited at the moment. If you have a question that is suitable for public consumption, then please feel free to post it here. If you have a question that is more personal in nature, please e-mail me at “halford@siumed.edu” and I will do my best to respond in a timely manner. Because I am often facing multiple deadlines at once, it is not always possible for me to respond right away.

    – Bill H.

  174. Thankyou foryourwork November 22, 2013 at 12:14 pm #

    Dr bill
    Is there any way we can contact you directly for more information on hopes for this vaccine?

  175. Bill Halford November 20, 2013 at 9:20 am #

    Dear Ole,

    Any one who tells you that you can remove HSV from your body either (1) does not know what they are talking about, (2) is well meaning but overly optimistic, or is (3) trying to sell you something. No, removal of HSV DNA from an infected person does not sound feasible to me, and I cannot believe that people receive funding for such ideas that sound like 99% science-fiction and 1% science.

    – Bill H.

  176. Ole November 20, 2013 at 8:09 am #

    So there ain’t no reason to belive that we can completly remove hsv from our body in the nearest future? Only slow down its outbreaks?

  177. Bill Halford November 19, 2013 at 9:53 pm #

    Hi Paul,

    I will have to take a look and do my homework before I can provide a detailed answer. However, in principle, yes I completely agree with your analysis that this would in principle be (1) a valtrex alternative and (2) might synergize with valtrex to provide a greater inhibition of HSV replication than is attainable with either drug alone.

    More options cannot be a bad thing, and this sounds like a reasonable possibility for a new antiviral drug against HSV.

    – Bill

  178. Paul Simpson November 19, 2013 at 7:00 pm #

    Bill ,

    we all some how missed the new antiviral Amenamevir. Its a helicase-primase inhibitor like AIC-316 and in phase 3 trials. This is good news for those of us that dont respond well to Valtrex. Yes?


    Some research shows it works better than Valtrex and some show it can be used with Valtrex for even better results. Maybe it will help us till your vaccine is ready for us.

    Any thoughts?

  179. Bill Halford November 19, 2013 at 12:29 pm #

    Yes, I think the vaccine will have therapeutic value to those already infected. This is addressed within one or more of the blog posts in some considerable detail, and numerous responses to earlier reader comments.

    – Bill H.

  180. Bill Halford November 19, 2013 at 12:27 pm #

    If you believe that DRACO is real, then I have some swampland that I want to sell you.

    DRACO = pie in the sky.

    Bottom line…..inhibiting virus replication in cultured cells (like DRACO does) is not anything remotely similar to the same as doing so in a living, breathing human being.

    – Bill H.

  181. Ole November 19, 2013 at 7:57 am #

    Hi Bill!
    What do you think about MIT’s Todd Rider research DRACO`?

  182. Ole November 19, 2013 at 4:13 am #

    What is your beliefs on MIT work on the DRACO?


  183. Andy November 19, 2013 at 12:18 am #

    As someone who has suffered from 2-4 HSV-1 and HSV-2 outbreaks per month for over 15 years I am hopeful there will one day be a better solution than the ineffective drugs currently available. Do you think the new vaccine will offer some type of relief for those previously infected or will this only help those who have had no exposure? Thank you for your work and your commitment to the greater good.

  184. Bill Halford November 18, 2013 at 10:23 am #

    Dear Beacon Street,

    Unfortunately, a 10-year timeline for the ACAM-529 vaccine to reach your doctor’s office is very reasonable.

    From a company’s point of view, it is reasonable that it would take some time to figure out if ACAM-529 is (1) well tolerated and (2) effective enough in (a) reducing the symptoms of GH or (b) preventing genital herpes to advance to full-scale production, marketing, distribution, etc. Even under the best of circumstances (i.e., in the fairy tale world of how I wish things worked), this would take a minimum of 3 years to sort out because there is a minimum of a 6-month lag time between injecting a person with a vaccine and assessing whether or not an adequate effect was observed. This is quite different from drugs that lower your cholesterol where an effect may be observed in 2 to 4 weeks.

    The complication as I have alluded to before is the FDA’s overreach to the point where they are effectively blocking / delaying / preventing existing HSV-2 vaccine technology described by scientists from being tested in humans. For example, the first papers describing the predecessor of ACAM-529 were published in the late 1990s……..the first person to be injected in a Phase I clinical trial of ACAM-529 will be injected in 2014…..that is a 15-year lag time just to start evaluating this HSV-2 vaccine, and yes it could easily take another 10 years to reach a doctor’s office. However, first things first……the question at the moment is (1) Is ACAM-529 safe enough? and (2) Does it reduce symptoms of HSV-2 genital herpes or prevent HSV-2 genital herpes? The safety question is the focus of Phase I, and is a no-brainer…..yes, it will be safe enough. The efficacy question is a different matter, and there we do need to wait on the results before we can assume that this is worthwhile enough to advance to a clinically-implemented HSV-2 vaccine.

    – Bill H.

  185. BeaconStreet November 18, 2013 at 9:18 am #

    Hi Doc: The ACAM-529 trial came up last night at a Boston herpes support group. None of us has a relevant science or medical background, but some of us have lived with HSV for decades. One of the more senior members suggested that a Phase I trial means a vaccine could still be more than a decade away (assuming ACAM-529 works and is deemed safe).

    Does that timeline seem sound to you?

  186. Bill Halford November 16, 2013 at 9:32 am #


    I wish that I knew when a HSV-2 vaccine would be available. I believe that we have a HSV-2 vaccine that will work in hand, but the FDA regulatory process is too busy saving us from ourselves to let me test my HSV-2 vaccine in you or anyone else.

    In general, the FDA regulatory process takes at least 10 years to navigate, and these days it seems like 20 years is pretty normal.

    Apparently the FDA thinks that it is OK for people to naturally get infected with wild-type HSV-2…..about 300 million people will be newly infected with wild-type HSV-2 over the next 20 years. What is not OK with the FDA is testing a new HSV-2 vaccine concept in people until $30 million dollars has been spent having lawyers (who often know very little about science) talk amongst themselves and agree that it is now OK to test a new HSV-2 vaccine.

    Wish I had a better answer for you.

    – Bill H.

  187. razi November 16, 2013 at 4:04 am #

    dr can i ask when hsv vaccine is available on market

  188. SC November 15, 2013 at 10:42 pm #

    Exactly the right amount of virology for this 3rd yr student currently swatting for exam next week. Too much virology is barely enough. Great to hear about the vaccine.

  189. Bill Halford November 15, 2013 at 5:50 am #

    Hi Staying Upbeat,

    This is hypothetically possible, but factually incorrect.

    You are correct that there are many serotypes of human papillomavirus……in excess of 100, and we call these human papillomavirus serotype 1, human papillomavirus serotype 2, human papillomavirus serotype 3, etc.

    In the case of herpes simplex virus, there are two serotypes…….herpes simplex virus serotype 1 (HSV-1) and herpes simplex virus serotype 2 (HSV-2). Like all viral serotypes, HSV-2 has evolved as a distinct serotype from HSV-1 so that it can still colonize people who already carry HSV-1. In essence, the difference between two viral serotypes rarely has anything to do with the addition or deletion of fundamentally new genes. Rather, HSV-1 and HSV-2 encode 75 homologous proteins that look different enough to the immune system (via small amino acid changes) such that an adaptive immune response against HSV-1 does not completely cross-protect against HSV-2.

    The comparison between herpes simplex virus and influenza virus is really apples and oranges. Herpes simplex virus is a very large dsDNA virus that encodes ~75 proteins; its genome contains ~153 kilobase pairs of double-stranded DNA. Its life cycle is a miracle of evolution, and reflects a highly evolved relationship between the virus, the cells it infects in the epithelium and the nervous system, and it has evolved a beautiful ability to roll over and play dead when cells of the immune system (T cells in particular) infiltrate virus-infected tissues. To suggest that the HSV genome could randomly undergo massive amounts of antigenic drift (genetic mutation) and still pull off this feat of nature is to completely misunderstand what an incredibly sophisticated / orchestrated piece of biology underlies the HSV life cycle. This is like saying that you can swap out the tires on a Formula 1 racecar for those from an old Toyota Corolla, and there will not be any loss in performance of your racecar.

    To the contrary, the HSV-1 or HSV-2 genome can tolerate remarkably few mutations that don’t destroy its ability to complete its life cycle in vivo, and thus random genetic mutation and antigenic drift are not an issue for HSV. Also, a second important aspect is that the rate of mutation of DNA-based viruses tends to be on the order of about 100,000-fold lower than RNA-based viruses like influenza virus. This is because DNA viruses replicate in the nucleus of our cells and have the benefit of the cellular proofreading machinery (i.e., exonucleases, mismatch repair proteins, DNA ligases) such that most misincorporations of the wrong base at a position in the HSV DNA genome tend to be corrected.

    In contrast, influenza virus like all other RNA viruses exist as what is known as a “viral quasispecies.” That is, influenza virus is an error-prone RNA virus that cannot access the cell’s DNA-based proofreading machinery, and thus almost every influenza virus virion that leaves a virus-infected cell differs by at least one nucleotide from the parent virus that infected the cell. To call a life form a “species” generally is to assume that the life form’s genome (nucleic acid sequence) remains relatively constant over time. Influenza viruses and RNA viruses do not by any stretch of the imagination look like a “species,” but rather look like a quasispecies that hovers around a consensus (average) genome sequence.

    Finally, influenza virus is a segmented RNA virus and every infectious virion carries 8 distinct pieces of RNA. Because of this genome structure, two influenza virions may infect the same cell in a pig, bird, or human and give rise to a completely new influenza virus that noone in the world has ever seen; this is called antigenic shift and is how new influenza viruses that carry unique combinations of the hemagglutinin (H) and neuraminidase (N) proteins are generated. Thus, when you hear about concerns of the next influenza pandemic caused by H5N1 influenza (or whatever the latest threat is), the H refers to the hemagglutinin protein and the N refers to the neuraminidase proteins that are the key glycoproteins on the surface of influenza virions.

    I imagine that is a little more virology than the average reader will appreciate. What I hope to convey is that there is a common misconception amongst vaccine scientists that a virus can be reduced to a collection of antigens, and if this is the case, then the viral subunit vaccine approach is a one-size-fits-all approach to preventing viral disease. However, the point I hope to make above is that each infectious agent has its own unique biology that merits attention, study, and consideration before we simply assume that 1 generic vaccine approach will work for all viruses.

    Bottom line: antigenic shift and drift are a major factor in how influenza virus vaccines need to be formulated, but these considerations are largely irrelevant to HSV-2 vaccines. Just like its kissing cousin, varicella-zoster virus, a single live-attenuated HSV-2 vaccine should suffice in preventing HSV-2 genital herpes without any concern for having to reformulate the vaccine over time due to viral mutations.

    HSV-2 is a wondrous feat of co-evolution between virus and host. This is its strength in terms of why it is so damned hard to control / get rid of with creams, antiviral drugs, etc. However, in the case of vaccines, this is HSV-2’s Achilles’ heel……if HSV-2 underwent random mutations in an attempt to escape an effective HSV-2 vaccine (as you propose), it would simultaneously lose its ability to complete an incredibly complex life cycle.

    – Bill H.

  190. StayingUpbeat November 15, 2013 at 1:01 am #

    Dr Halford,
    Why is it that when developing vaccines for viruses like HPV and influenza a different formulation is required to be effective for each sub-strain but one formulation can be reasonably expected to be effective for all sub-strains of HSV-2?
    It seems like with how long HSV has been in the population there would be a lot of massively different sub-strains that would need to have their own deletion mutant developed and included in the mix.

  191. Bill Halford November 14, 2013 at 11:04 pm #

    Hi David,

    Personally, I am not impressed with Corridon / Dr. Frazier’s efforts in the realm of HSV-2 vaccines.

    What I have seen to date is a lot of hype, press releases, and all the standard vague talk of raising money for Corridon’s efforts.

    Dr Frazier’s group could easily change my opinion by publishing some results, and telling me about the science behind what they are trying to achieve. However, when all I hear are lots of press releases, and these are not balanced by scientific publications, then I start to have doubts. That is where I am with Dr. Frazier’s work.

    A scientific publication on the topic should (1) introduce what has previously been done with HSV-2 vaccines, (2) offer an alternative solution, (3) offer proof that the alternative solution works, and (4) describe the detailed methods regarding how the alternative solution works.

    To date, Dr. Frazier’s group has not addressed these questions in a detailed and substantive manner that convinces me that there is some real science behind their money-raising efforts. Hopefully they will prove me wrong soon.

    – Bill H.

  192. David Ramirez November 14, 2013 at 10:01 pm #

    What is your opinion about the Australian trials currently being conducted by Dr. Ian Frazer? He seems to be on the right path and there are many positive articles regarding his approach. Thank you.

  193. Bill Halford November 14, 2013 at 6:24 pm #

    Hi Mat,

    It is my privilege to have the opportunity to do so. I would hope that more of my colleagues in the sphere of NIH-funded research would more often remember that “the common people” / U.S. taxpayers are the very people who are paying the bills that allow us to play in the laboratory and figure out how the natural world works. Thus, it is not just our job to figure out the science, but also to relay the take-home message back to the people who are paying the bills. Without the U.S. taxpayers’ support, I would not have published a single scientific paper in my career nor would I currently hold my current position teaching medical students about infectious disease. This blog is a small way of paying back the debt I owe to those who supported my research.

    – Bill H.

  194. Mat November 14, 2013 at 5:44 pm #

    Thank you Dr. Bill. You are the people’s Dr. You bring science and hope to the common people.


  195. Bill Halford November 14, 2013 at 12:14 pm #

    Hi Mat,

    Yes, I believe the ACAM-529 vaccine holds more promise that the DISC vaccine by Cantab for two reasons.

    First, I think that it is overly simplistic to say that the ACAM-529 vaccine and Cantab’s DISC vaccine are exactly the same. Among other things, the HSV-2 ACAM-529 vaccine contains different mutations in the viral genome than the HSV-2 glycoprotein H mutants that were the basis of the DISC vaccine. Also, of critical importance, is that viral vaccine efficacy will be dependent upon the number of infectious units of virus in each injection. It appears to me that Sanofi Pasteur has invested a lot more time and effort into developing the ACAM-529 vaccine formulation, and part of that could be a 10- to 100-fold higher dose of HSV-2 ACAM-529 vaccine in the target dose that they will be putting into human clinical trials. Bottom line is that Cantab’s DISC vaccine failure does not automatically mean ACAM-529 will meet the same fate. ACAM-529 is a new HSV-2 vaccine, and it is much better documented in the published literature has producing robust protection in animals than Genocea’s GEN-003 vaccine or Agenus’s HerpV vaccine. In my opinion, ACAM-529 represents the first HSV-2 vaccine to advance to human clinical trials in 10 years where the available evidence indicates that it is likely to achieve a beneficial effect in vaccine recipients, and reduce a vaccine recipient’s relative risk of HSV-2 genital herpes.

    The second and perhaps more important reason that the HSV-2 ACAM-529 vaccine is different is because the scientific community is now ready (mentally prepared) for the possibility that Herpevac might not be adequate to stop the spread of HSV-2 genital herpes. When I first started writing grants on a live-attenuated HSV-2 vaccine in 2006, reviewers would often tell me that the investigation of a live-attenuated HSV-2 vaccine was a waste of time. The rationale they offered generally went something like this…..
    1. We already have a promising HSV-2 vaccine in Phase 3 clinical trials called Herpevac;
    2. Once Herpevac succeeds in clinical trials, it will advance to the marketplace and genital herpes will be a disease of the past;
    3. Herpevac is a very safe, glycoprotein D subunit vaccine;
    4. Why in 2007 would we waste our time studying a more dangerous live-attenuated HSV-2 vaccine that is simply going to achieve the same goal that the Herpevac vaccine currently satisfies…..a safe and highly effective HSV-2 vaccine.

    Fast forward 7 years….
    Herpevac did not work and numerous labs have independently found that HSV-2 viral vaccines are vastly superior to glycoprotein D subunit vaccines. At this point in time, I am sure that there are still true believers in the glycoprotein D subunit vaccine, but the scientific writing is on the wall that HSV-2 viral vaccines are clearly superior.

    So, getting back to your question about Cantab’s DISC vaccine…..when Cantab ran their DISC vaccine trials in the late 1990s and early 2000s, the overwhelming narrative and belief system of scientists was that (1) a DISC vaccine was redundant with Herpevac and (2) a glycoprotein D-based subunit vaccine was preferable for regulatory and manufacturing reasons. When such a bias is predominant in science, it is hard for any approach to succeed / move forward in the face of such a headwind.

    In 2014, based on the available evidence that was published between 2008 and 2013, I just don’t think anyone can legitimately suggest that ACAM-529 is the same thing as Herpevac. Now that we recognize that glycoprotein D subunit vaccines are not the final solution to the HSV-2 genital herpes problem, I believe that we are ready (mentally prepared) to more honestly evaluate whether a DISC vaccine approach such as ACAM-529 might achieve a more favorable result. I am optimistic that it will, but caution that attenuating HSV-2 by virtue of eliminating its capacity to replicate and engage in viral DNA synthesis might also attenuate the full immunogenic potential of a whole HSV-2 viral vaccine.

    So, I agree that a replication-defective HSV-2 vaccine may not represent the final solution to our HSV-2 genital herpes problems, but I note that it is a profoundly huge step forward relative to what we have been doing for the past 10 years, and for that I am truly grateful.

    – Bill H.

  196. marylupino November 14, 2013 at 8:51 am #

    http://www.privateherpesdating.com/login?u=%2Fupgrade%2Fthankyou%3F__utma%3D1.421696989.1384262826.1384269066.1384301048.3%26__utmb%3D1.6.7.1384301050583%26__utmc%3D1%26__utmx%3D-%26__utmz%3D1.1384301048.3.3.utmcsr%253Dmembership_free%257Cutmccn%253Dnl_veteransday_2013%257Cutmcmd%253Demail%26__utmv%3D-%26__utmk%3D178234277 Dear Doctor
    This is the website for herpes dating that I have started using. Maybe there will be some way of conjuring up support for the trial with some of these folks. Just a thought. God bless and keep up the fight, and do not forget the other diseases that herpes can lead to such as encephalitis etc …
    Mary Gatt

  197. marylupino November 14, 2013 at 8:45 am #

    Dear Doctor
    Unfortunately, my age prevents me from being the volunteer for the study. I am 62. I know there are follow-ups needed, so maybe I would be dead already. Please let me know if exceptions can be made. Maybe the vaccine would be too much for an old bat. Anyway I will continue to feed my ideas to you. Sincerely, Mary Gatt

  198. Mat November 14, 2013 at 4:04 am #

    Hi Dr. Halford,

    Do you think this vaccine holds more promise than the DISC vaccine by Cantab?

    Thank you,