Purpose of the Herpes Vaccine Blog


June 15, 2013 |

WHO AM I?

My name is Bill Halford and I am an Associate Professor of Microbiology and Immunology at Southern Illinois University School of Medicine in Springfield, Illinois.  I have studied herpes simplex virus (HSV) biology since 1991, and I became interested in trying to develop a safe and effective HSV-2 vaccine in 2006.  There are at least 100 individuals in the world who are actively pursuing a HSV-2 vaccine, and I am one of these many researchers.  In this blog, I will try to cut through the nomenclature and statistics and explain in relatively straightforward terms what we know about HSV-2 vaccines and what we need to do next to advance a safe and effective HSV-2 vaccine to human clinical trials.  If you wish to contact me, you can do so via this blog or e-mail me at “halford@siumed.edu.”

 

DISCLAIMER

The author of this website, Bill Halford, is an employee of the Southern Illinois University School of Medicine in Springfield, Illinois.  The viewpoints expressed on this website are solely that of the author, and should not be construed as an official statement of the policies, procedures, or opinions of Southern Illinois University, the School of Medicine, or any of the academic departments contained therein.

 

BACKGROUND ON HSV-2 INFECTIONS AND GENITAL HERPES

Genital herpes caused by herpes simplex virus type 2 (HSV-2) remains a huge medical and public health problem.  About 1 billion people (out of ~7 billion total) are life-long carriers of the HSV-2 virus.  About 40 million of those HSV-2 infected persons live with genital herpes outbreaks that recur once every 2 to 12 months over the duration of their lives.  Each outbreak can last from 2 to 20 days in duration, and is physically uncomfortable and emotionally distressing.  Antiviral drugs such as acyclovir or valacyclovir (valtrex) reduce, but do not prevent. the symptoms of recurrent genital herpes.  Likewise, antiviral drugs have not slowed the spread of HSV-2 infection at all; ~20 million per year continue to acquire new HSV-2 infections from the 1 billion people who already carry the HSV-2 virus.

HSV-2 genital herpes has been described as a silent epidemic.  This term is apt, as HSV-2 exists all around us and is carried by friends and family members, but people are reluctant to disclose that they are infected with HSV-2 as there remains a historical stigma associated with this infection.  Many people who have the HSV-2 virus have not had many sexual partners, and many teenagers who acquire HSV-2 have the misfortune of acquiring HSV-2 with their first sexual partner.  Nonetheless, the social stigma that people with HSV-2 wish to avoid is the perception that they have slept with dozens of people.  For this and a variety of other reasons, the ~200 million people who have experienced symptoms of HSV-2 genital herpes do not tend to share this information with many people.  Thus, it is hard to estimate the magnitude of the problems caused by HSV-2 genital herpes.  One number helps put the problem into perspective; each of our children has a 1-in-10 chance of contracting a HSV-2 infection before they are married.

Aside from the individual suffering caused by recurrent genital herpes, HSV-2 infections can cause more severe complications such as HSV-2 infections of newborns as they pass through the vagina / birth canal.  The immune system of neonates is not yet developed, and thus HSV-2 infections in newborn babies can be devastating often resulting in death or severe mental / cognitive impairment, as HSV-2 infection can spread to the central nervous system of newborns.

Bill Halford

 

THE POTENTIAL UTILITY OF A HSV-2 VACCINE

Effective vaccines have been responsible for the eradication and/or control of many viral diseases such as smallpox, yellow fever, red measles, mumps, German Measles, hepatitis B, chickenpox, and poliomyelitis.  In principle, there is no reason that a safe and effective HSV-2 vaccine could not be deployed in the human population to prevent HSV-2 genital herpes.

The applications of a safe and effective genital herpes vaccine would be two-fold.

First, an effective HSV-2 vaccine could be given to adolescents or prospective sexual partners of those who already carry the HSV-2 virus.  Exposure to an effective HSV-2 vaccine would bolster the immune system of such individuals such that their bodies were at least 100 times better prepared to repel the real (wild-type) HSV-2 pathogen if they were exposed later in life.  Such a “preventative HSV-2 vaccine” could be used to prevent ~20 million per year from newly acquiring the HSV-2 virus.

Second, an effective HSV-2 vaccine could be given to those who suffer from frequent outbreaks of recurrent genital herpes.  Such a “therapeutic HSV-2 vaccine” could be used to reduce the frequency and duration of genital herpes outbreaks in those ~40 million people worldwide who suffer from this chronic viral disease.  This latter application of a HSV-2 vaccine (i.e., to reduce symptoms in those who already carry the HSV-2 virus) would be more experimental, and less of a sure thing than a preventative HSV-2 vaccine.  Nonetheless, there are several publications dating back to the 1950s that claim such an effect has been obtained by treatment with a variety of vaccine formulations including inactivated-preparations of HSV virion particles.  Therefore, once a safe and effective HSV-2 preventative vaccine is identified, it will be relevant to determine if it has potential  to also serve as a therapeutic HSV-2 vaccine.

 

WHY DO WE STILL LACK AN EFFECTIVE HSV-2 VACCINE?

This is the million dollar question, and will be precisely the focus of the Herpes Vaccine Blog.

I envision posts on the Herpes Vaccine Blog serving one of three general purposes, and these will be discussions of:

1.  The science of HSV-2 vaccines

2.  Moving a safe and effective HSV-2 vaccine into human trials

3.  Answers to specific reader queries (which may be sent to halford@siumed.edu)

 

What I hope to make clear through the development of this blog is that a safe and effective HSV-2 vaccine lies within our grasp, but what we lack is a critical mass of support to advance such a HSV-2 vaccine to human clinical trials.  The primary barriers to the advancement of an effective HSV-2 vaccine are (1) misinformation and (2) a pre-conceived notion that certain types of HSV-2 vaccines (e.g., live-attenuated) should not be investigated or considered for use as a human vaccine.

One of the central purposes of this blog will be to (try to) simply explain why past HSV-2 vaccines have not worked, and define what we need to do differently in the future if we intend to end the needless suffering caused by genital herpes.  Make no mistake…..HSV-2 genital herpes is a vaccine-preventable disease.  However, the field of HSV-2 vaccine research is long overdue for a “course correction.”  I hope that this blog serves as a vehicle to increase the public’s understanding of what we need to be doing differently if we hope to make HSV-2 genital herpes a disease of the past.

– Bill Halford

 

76 Responses to Purpose of the Herpes Vaccine Blog

  1. faith in God November 1, 2014 at 11:19 am #

    Hello Dr. Halford, I respect you so much! You seem to be a very caring person, and can tell you are a very humble and down to earth person. I wish nothing but good for you and your family. I praise the type of person you are. Dr. Halford, I was just wondering, if you have considered performing trials in Mexico or any other country you would be comfortable with? In Mexico you wouldn’t be under FDA scrutiny; from what I understand. You can set up lab there at a rather inexpensive cost versus here in the US. To give you an idea, if you were to raise $100,000 for a lab in Mexico it would equal to having $1,000,000 in the US. Believe me people who suffer from this terrible disease will make the trip down to Mexico for a potential cure!! You can hire Mexican labor such as big corporations do; in order to save cost. I know it may sound far fetched and unrealistic but so are the FDAs demands and ignorance. I believe you can do it. I would even give you a helping hand; I have a medical background and speak the language. Not all parts of Mexico are a nightmare. IDK, if a phase 1 trial were to be performed there sometime next year, it would mean so much for so many. Maybe during your Summer break or something. Thank you once again, for all your information and for all you do. You are heaven sent.

  2. Peter October 17, 2014 at 11:17 am #

    I also have had success w the VZV vaccine for my HSV1 outbreaks.
    After my 1st vaccination I was free of outbreaks for 4 years.
    I was revaccinated over a year ago and have had only 2 outbreaks so far.
    Incidentally, my outbreaks are quite severe, with ocular involvement.
    Dr Halford has been very helpful in sharing his learnings w lay people like myself.
    I have found most family doctors are not that informed re HSV1, so Bill’s advice has been invaluable.
    Bill, thank you so much! And here’s wishing everyone w HSV that Dr Halford continues to work on getting approval for his research!

  3. Amanda October 16, 2014 at 9:16 pm #

    I’ll be ur Guinea pig lol I read about how successful your vaccine is in animals online..next step humans..anything is better then living with this! I feel like lack of funding is stopping the cure/vaccine, that and big companies/pharmaceuticals do not want to loose out on all the money they are making from the suppressant drugs. I want to thank you for your hard work in finding a cure/vaccination for this virus.
    I also read this :
    http://www.researchgate.net/publication/236963380_Efficacy_of_the_anti-VZV_(anti-HSV3)_vaccine_in_HSV1_and_HSV2_recurrent_herpes_simplex_disease

    Taking the anti-varicella zoster virus (anti-VZV, also known as anti-HSV3) vaccine (ckn pox vaccine) against orobuccal herpes simplex virus type 1 (HSV1) and genital herpes simplex virus type 2 (HSV2). Does not cure the virus but stops outbreaks.
    From 2005 through 2011, for the 24 anti-VZV vaccinated patients, the average number of herpes relapses decreased to 0, correlated with an increased anti-VZV antibody level and of herpes relapses decreased to 0, correlated with an increased anti-VZV antibody level and clinical recovery of all patients, whereas no improvement was observed for the 26 non vaccinated herpes patients.
    Seems promising …since its a live strain as well….what do you think….lack of funding has stopped this study too….I just really wish for a cure/vaccine for the stopping of outbreaks(they r horrible)..and not having to worry about the life long expensive cost of med (which I am glad I have at least something to lean on ) .
    http://en.wikipedia.org/wiki/Herpes_simplex_research
    Thank you for your hard work and dedication to fighting this horrible virus.
    Amanda :)

    ABSTRACT Background: The aim of this study was to evaluate the possibility of using the anti-varicella zoster virus (anti-VZV, also known as anti-HSV3) vaccine against orobuccal herpes simplex virus type 1 (HSV1) and genital herpes simplex virus type 2 (HSV2). This was suggested by study of the phylogenetic tree of members of the herpes virus family, which showed a close relationship between VZV (HSV3) and the HSV1 and HSV2 herpes viruses.
    Methods: The present prospective study was conducted from January 2005 through January 2011. Twenty-four patients afflicted with HSV1 and HSV2 herpes recurrences over a period of years, numbering 6–8 and more recurrences per year, agreed to receive the anti-VZV vaccine. They were compared with 26 nonvaccinated patients presenting with herpes simplex diseases 2–5 times a year. All 50 patients were documented with anti-HSV1, anti-HSV2, and anti-VZV antibody serological testing.
    Results: From 2005 through 2011, for the 24 anti-VZV vaccinated patients, the average number of herpes relapses decreased to 0, correlated with an increased anti-VZV antibody level and clinical recovery of all patients, whereas no improvement was observed for the 26 nonvac- cinated herpes patients.
    Conclusion: Data for the anti-VZV serological antibody levels tested before and after anti- VZV vaccination showed a significant (P , 0.001) increase among vaccinated patients. This suggests defective anti-VZV immune power in these patients. After 6 years of positive results for anti-VZV vaccine, this is a logical and fair hypothesis. We can now undertake a randomized study to confirm these findings.

  4. Jonathan September 29, 2014 at 8:17 pm #

    Dr. Halford:

    What, specifically, would it take to take your live, attenuated vaccine, to human trials? How much money are we talking here, and would you attempt to do it here, or in another country where it might receive a more favorable research climate?

    Best,

    Jonathan

  5. Bill Halford September 21, 2014 at 2:14 pm #

    Hi Kim Olav,

    As a whole, I think a live- and appropriately-attenuated HSV-2 vaccine is the only viable HSV-2 vaccine strategy. Period. End of sentence. This is the approach that led to an effective chickenpox vaccine per the live-attenuated VZV Oka vaccine. I note that HSV-2 and VZV share ~60 viral genes in common and a similar lifestyle of establishing life-long latent infections in neurons, where the virus may remain latent and later reactivate (to cause shingles in the case of VZV).

    Vical is not a live-attenuated HSV-2 vaccine, and hence I am not optimistic that it will succeed.

    ACAM-529 is a whole HSV-2 vaccine, but I am concerned that ACAM-529 may not be “appropriately attenuated,” but rather may be overattenuated because it cannot replicate in vaccine recipients. Not once in the history of mankind has a non-replicating virus, like ACAM-529, been used to effectively prevent / vaccinate against a viral disease. If ACAM-529 succeeds, it will be the first such “replication-defective virus” vaccine to do so.

    Live- and appropriately attenuated-viral vaccines have been used to prevent smallpox, yellow fever, poliomyelitis, measles, mumps, rubella, shingles, and rotavirus-induced diarrhea. I like the track record of live viral vaccines…..they always succeed provided that they are appropriately attenuated (not too much / not too little).

    You can ask about every HSV-2 vaccine approach that has ever been mentioned and/or advanced to a human clinical trial. My response will not waiver until I see hard evidence to the contrary. The available scientific evidence continues to suggest that only a live- and appropriately attenuated-HSV-2 vaccine will succeed, and thus I continue to search for a path to take my lab’s live HSV-2 vaccine forward to a human clinical trial. Perhaps the Vical trial based on immunization with pieces of HSV-2 (not the actual HSV-2 virus) will yield a different result, but I am not optimistic based on the success rate of past HSV-2 vaccines that introduce vaccine recipients to only small pieces of HSV-2.

    – Bill H.

  6. Kim Olav Lunde September 21, 2014 at 1:09 pm #

    Hi Bill.

    But where do we stand this days with the HSV-2 vaccine and l do mean the hole industry ? and where are you now on your HSV-2 vaccine , do have something that may work or?
    And what is the deal with Vical?:
    A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Phase 1/2 Trial to Evaluate the Safety and Efficacy of Herpes Simplex Virus, Type 2 Therapeutic DNA Vaccines in Symptomatic HSV-2-Seropositive Adults. For more information, please go to the NCT02030301 trial listing at ClinicalTrials.gov. ​

  7. Bill Halford September 21, 2014 at 12:31 pm #

    Dear E,

    You essentially asked “Why so much pushback regarding a live-attenuated HSV-2 vaccine when it is the most logical solution, and in fact may be the only approach that is likely to stop the spread of HSV-2 genital herpes in the human population?”

    After asking the question, you postulate / ask that perhaps greed is the underlying motivation based on the conspiracy theory idea that drug companies like having a population of tens of millions of people who could potentially take valtrex every day. The staggering number of people who have active genital herpes disease accounts for why valtrex alone is a $1.2 billion per year drug.

    The greed hypothesis assumes that the scientific community (as a whole) has their act together enough to (1) agree upon the most logical path forward to prevent HSV-2 genital herpes with a vaccine, but (2) is actively suppressing the deployment of this vaccine technology. Let me reassure you that this is NOT TRUE, and is not the root cause of why we continue to lack a HSV-2 vaccine.

    Although greed is a powerful potential incentive, the real explanation is far more banal and boring and is the same root cause of most of the USA’s problems…….the powerful double-whammy combination of (1) profound ignorance and (2) intellectual arrogance amongst our so-called leaders. Every person has blind spots in their existing knowledge database, and so do effective leaders. However, effective leaders (in a democratic society) are not afraid to admit where the boundaries of their understanding lie, and hence they LISTEN when people who are better informed on a specific, small topic approach with a logical and cohesive argument that suggests, perhaps, a change in policy or approach may be warranted. However, most of the FDA / NIH leadership seems to run on CYA-based decisions, rather than logic-based decisions, which dictate that it is effectively better to maintain the status quo of HSV-2 vaccine research (unlikely to succeed, but will not ruffle anyone’s feathers) rather than risk backing a new live-attenuated HSV-2 vaccine (more likely to succeed, but fraught with political danger and blow-back from the FDA).

    For the past 35 years, the leadership of the FDA, NIH, and Department of Health and Human Services has adamantly maintained that a “live-attenuated HSV-2 vaccine would be too dangerous to investigate or deploy in the human population,” and so we have opted for so-called “safer” HSV-2 subunit vaccines like Herpevac that have failed in six human clinical trials spanning the past 25 years. Genocea’s GEN-003 and Agenus’s HerpV vaccine appear to be on track for similar costly and time-consuming (time-wasting) failures. In my estimation, the leadership of the FDA and the NIH has little interest in reconsidering the wisdom of a 35-year-old policy to deliberately avoid research / investigation that could lead to the development of a live-attenuated HSV-2 vaccines. In part, this reflects a failure to consider the FACT that live-attenuated HSV-2 vaccines can be produced that are very safe. The other part of the equation boils down to intellectual arrogance, and reticence amongst the FDA and NIH to take ownership of the consequences of a HSV-2 vaccine subunit development “strategy” that has been consistently failing for the past 30 years.

    Over 300 million people such as yourself have been newly infected with wild-type HSV-2 while the NIH and FDA have been blithely testing HSV-2 subunit vaccines for 30 years, and simultaneously refusing to advance a single live-attenuated HSV-2 vaccine to a human clinical trial. I would suggest that our leaders at the NIH and/or FDA should educate themselves on the FACTS that clarify why a live-attenuated HSV-2 vaccine is highly safe and feasible, and is ~100 times more effective (both in theory and practice) at preventing HSV-2 genital herpes.

    In my estimation, our continued lack of an effective HSV-2 vaccine stems from poor leadership within the scientific community, rather than greed. After 30 years of HSV-2 subunit vaccine failures, perhaps there will be a new willingness within the scientific community to consider the logical alternative that a live- and appropriately-attenuated HSV-2 vaccine might actually stop the spread of HSV-2 genital herpes in the human population, it it were only taken off of the sidelines and advanced to a human clinical trial.

    – Bill H.

  8. E September 21, 2014 at 11:48 am #

    Hi Dr. Halford,
    I suffer from HSV2. The stigma from society and the emotional as well as physical damage it has done to me is a hard thing to deal with. I am currently taking a human pathophysiology class and we are discussing vaccines. From the readings and discussions, it seems to me that a live attenuated virus is the best option for preventing infections. Can you tell me why the government does not support you on your vaccine, even though you have had great success in animal trails? I know the likelihood of causing a herpes infection from a live attenuated virus vaccine is extremely minimal and would do a lot more good that bad (as seen with the polio live attenuated virus vaccine). If I had a ton of money I would donate it to you so you could move this vaccine to human clinical trials. I could be wrong, but I feel like the pharmaceutical companies don’t want a preventative vaccine for herpes because it would be a one time shot, versus having only therapeutic vaccines would mean continuous booster shots for those infected. Everything seems to boil down to money. Maybe if greed wasn’t so common these days, I would have already had a preventative vaccine for this before I became infected a couple of years ago (but that is just my opinion).

  9. Billy August 3, 2014 at 10:04 pm #

    It has been phenomenal to read the actual thoughts and workings of one of the premier authorities on the matter of HSV reduction and eradication. I have been suffering with HSV2 for the last 12 years of my life, and had that person informed me they had it, I would have been one of the few understanding souls she had encountered. Instead, she set out to ensure I contracted it being that she wanted to guarantee a permanent place in my life. She achieved her goal, but I am sure she intended to be at my side, rather than in my rear view as she stands today. I have infrequent recurrences which appear between 4 to 6 times annually. I would be more than willing to sign a release and take part in your trials. I know you said that there is little evidence to support a suppression of these trials and drugs from proceeding, but I am very observant and have reservations. Treatment has seemingly become the desired outcome of most of big pharms research, versus curing disease. Obviously, there would be a much greater return on any investment that is perpetuated by permanence. I look about, and it seems that erectile dysfunction has been more important than curing diseases such as HSV. I am just happy to know that someone somewhere realizes how important to humanity such a vaccine would be. I can only imagine how many people would have escaped HIV infection, or even not contracted a lesser STI or venereal disease had they not had an open, virus-laden lesion come in contact with their flesh. I thank you good doctor for all that you do. Godspeed my friend!

  10. Tim July 24, 2014 at 11:15 pm #

    I know it us off the subject ….. But could you develop a parvovirus b19 vaccine ?

  11. Pritelivir July 24, 2014 at 9:03 am #

    I did not realize that mutations within the same protein can make or break an efficacious vaccine. Have you published this information?

  12. Mark July 14, 2014 at 10:10 pm #

    Hi Bill

    Find out anything on Nanobio NB-001 cream. Seems to have disappeared!

    Also, found another topical solution that states it works on outbreaks but was wondering if what they are stating is true!
    Found this on a website reviewing Dynamiclear but did not see this terminology on their website (though it eluded to it).
    http://choraphorreview.com/
    http://dynamiclear.com/

    “Dynamiclear works by destroying virus particles on impact, which affects both the initial outbreak that is treated as well as future episodes.

    The fact that the herpes virus will retreat into the nervous system makes it extremely difficult to eliminate completely. What can be done is to attack the virus every time that it surfaces, depleting it with each encounter and diminishing the amount of virus retreating back into the nervous system.”

    Not sure how treating the outbreaks would diminish future outbreaks or impact the latent reserves. The virus replicates in the nerves, so these reservoirs are always there.

    Also, was wondering what your take is on Vical’s HSV vaccine. Seems like a good step until something better comes along.
    http://www.vical.com/products/infectious-disease-vaccines/HSV-2-vaccine/default.aspx

    As for your vaccine approach and AuRx vaccine, they seems very similar. Was wondering why someone else can’t pick up where they left off. It would be in Phase 3 trails. Seems the laws need to change so if a company goes out of business (or shows no desire to continue to do the research like Amgen buying Biovax), another company can start their research where the last company left off. This would definitely speed up research.
    Just an idea, but would take someone with influence to push it through!

    Lastly, I see you take donations. I did not see any listing of how much people have donated to date. It would be nice, and may bring in more donations, if there was a set amount your are striving for and how much has been donating to date (maybe the Gates foundation would donate too if you wrote them).

  13. Expertonnose June 2, 2014 at 1:41 pm #

    Nanobio has currently a nasal vaccine against HSV-2 in pre-clinical stage, I think it’s called NE80-gD2.

  14. Bill Halford June 2, 2014 at 7:37 am #

    Hi Mark,

    Thanks for filling me in……NB-001 definitely slipped under my radar. I will look into it in the coming weeks, and reply with regard to what I find.

    – Bill H.

  15. Mark June 1, 2014 at 10:19 pm #

    Hi Bill

    NB-001 was a cream used to treat hsv once symptoms occurred. It is suppose to be as effective as acyclovir without the side effects. It completed 2 phases with successful results and looks like it completed Phase 3 studies last summer. Some members from a different board were involved in the study and mentioned it worked well. Found it strange that all info was taken down about this technology and now they are pursuing a vaccine instead. CEO left to work for Merck and now they have a license agreement to work on vaccines with Merck (seems personal goals may have killed this technology). GSK had actually licensed this technology (suppose to be the next gen Abreva since patents are running out).

    Just wondering if that would mean a failure of Phase 3 or since no results published, are they still looking at data?

  16. Bill Halford May 29, 2014 at 7:05 pm #

    Hi Mark,

    Thanks for your inquiry. I must confess that I had not heard of the “Aurx vaccine” before (http://www.aurx.com/), but upon reading more I realize that I know it by a different name in the HSV-2 vaccine literature. This appears to have been an attempt to commercialize / test the HSV-2 ICP10PK vaccine developed in Laurent Aurelian’s lab in the late 90s / early 2000s. I cannot say that I know a great deal about the pros and cons of the live HSV-2 ICP10PK vaccine, but I agree that in principle it is similar to my lab’s live-attenuated HSV-2 vaccine, but a different attenuating mutation has been inserted into the HSV-2 genome. I would have to test the two live HSV-2 vaccines (i.e., my lab’s HSV-2 0deltaNLS versus Dr. Aurelian’s HSV-2 ICP10PK) in a side-by-side fashion to comment on how they compare in the particulars of (1) safety profile / attenuation and (2) efficacy. On paper, they are two parallel strategies to achieve a similar goal. I note that the information on the website seems to provide yet more anecdotal evidence that a HSV-2 therapeutic vaccine is possible. I have a pending blog post that I intend to write on precisely this topic, but I simply have not had the time to complete this post……hopefully I will get it completed and posted by late June 2014.

    The HSV-2 Immunovex vaccine developed by Biovex (since purchased by Amgen) appears to my eye to be an over-attenuated live HSV-2 vaccine. That is, when you are trying to attenuate a virus to “make it safe” (i.e., reduce its capacity to cause disease), it is possible to go too far such that the “overattenuated” live HSV-2 vaccine does not deliver an adequate stimulus to the human immune system to elicit long-term protection. This is an obvious potential problem with the HSV-2 Immunovex vaccine which is entirely deleted of either 4 or 5 HSV-2 genes. In contrast, the Aurx vaccine you cite above contains a mutation in a single HSV-2 protein (the large subunit of HSV-2’s ribonucleotide reductase) and my lab’s HSV-2 0deltaNLS vaccine carries two in-frame deletions in a single HSV-2 protein, ICP0. I can tell you from my experience constructing nine different HSV-2 ICP0- mutants (i.e., 0delta104, 0delta125, 0delta127, 0delta129, 0delta254, 0delta810, 0deltaRING, 0deltaNLS, and 0deltaMD), the biggest problem I ran into is that even though I was only mutating a single HSV-2 protein, 5 of the 9 ICP0- mutant viruses were grossly overattenuated and would have been useless as HSV-2 vaccines. Only 2 of the 9 HSV-2 vaccine constructs (0deltaRING and 0deltaNLS) were both 1. highly attenuated (unable to cause disease) and yet still retained the capacity to 2. stimulate a HSV-2-specific immune response and hence serve as a highly effective live HSV-2 vaccine. Against this background regarding the technical challenges of deriving an appropriately attenuated HSV-2 vaccine, any multi-gene deletion such as HSV-2 Immunovex strikes me as unlikely to succeed. Arguably, HSV-2 ACAM-529 may ultimately exhibit similar limitations as it is a dead (non-replicating) virus; it is, by definition, impossible to attenuate a virus to any greater extent than to complete destroy its capacity to replicate / propagate in vaccine recipients.

    Nanobio…….sounds like a germicide. If I am correct in this assumption, I fail to see how a germicide could be used to effectively reduce rates of HSV-2 transmission or disease. I would assume that condoms would be equally effective, or more effective, at reducing the risk of HSV-2 transmission than a germicide in the real world of how sexual encounters go (i.e., no scientist is sitting around carefully painting germicide on you and your partners’ bits before you get down to business).

    – Bill H.