Halford HSV-2 Vaccine Research Highlights

Since setting up this blog in June 2013, I have received several inquiries about how my research fits into the broader topic of the field of HSV-2 vaccine research.  To address such questions in advance, I provide a brief summary below.

For anyone interested in all the details, a quick visit to PubMed (http://www.ncbi.nlm.nih.gov/pubmed) followed by entry of the search term “Halford W” will pull up everything I have published on the topic.

For anyone who wishes to donate to my lab’s research efforts to find a HSV-2 vaccine, I provide the relevant information at the bottom.

– Bill H.


1.  Bill Halford’s 2007 Future Virology Editorial on HSV-2 vaccines:



2.  Karen Carlson’s 2010 Aspects magazine article:



3.  Lachlan Whatmore’s 2010 Diffusion Science radio show interview:


4.  Dean Olsen’s 2010 State Journal Register newspaper article:



Anyone interested in making a tax-deductible donation to the Halford Vaccine Research Program may do so by mail, as follows:

Write a check payable to “SIU Foundation” and either in a letter or on the Memo line of the check write “Halford Vaccine Fund,” and mail the check to the following address:

Mrs. Risa Kirkpatrick, Business Administrator
Dept of Microbiology and Immunology
Southern Illinois University School of Medicine
P.O. Box 19626
Springfield, IL 62794-9626

These funds will be used solely for the purposes of HSV-2 vaccine research.

Please note that while Online Donations to the SIU Foundation are technically possible, I can only personally assure that donations to the SIU Foundation are properly allocated into the Halford Vaccine Fund if they are mailed directly to my Departmental Business Administrator per the instructions above.


  1. Hi Bill,

    Hope you are doing good, no new posts from a long time seems very busy, how u going with your research & funding, I would like to request to people here please donate for this noble cause, Bill any hope for us in near future 2-3 years from now

  2. Dear Bill

    I can assure you many infected people would play Russian roulette where if they survive they would be rid of this disease. They would not care about a 0.1% or 2% chance of serious complication..(I know the FDA would ).
    Have you considered crowd funding. I am sure you could get 50 million $ together. You have a track record that goes back to 2007. In two years there would have been too many failed crowd funders- some with bogus research which they are producing right now. .and getting this money together on crowd funding might not be easy anymore.

    People saw in the news with their own eyes how an experimental drug saved Ebola infected people, yet was years from getting released.. because it is life and death situation. Maybe I would rather have Ebola. At least I would have a chance to get cured!

    You could also try and get approval in other countries like UK / Scandinavia etc. The FDA is too careful with this diseases. This disease is different , doctors are terrible at diagnosing it. Standard STD tests do not test for it!!
    Too many people pass it on unknowingly.. Those that know suffer those that are ignorant not…The knowledge comes from the internet not from the doctors!! ( My doc said 99% it is not HSV, I could have passed it to 3 people had I not been so suspect.)

    It is a diseases that is potentially killing economies. In many developed countries 20% to 25% of the women of child bearing age are infected and another 16% to 20% of men in the age of wanting to settle down.. Imagine if just a 1/3 are aware . The number of people in relationships that can no longer enjoy unprotected sex and the number of relationships that are never formed, and the number of people the quit the dating game completely. The first unplanned child that brings two people from a relationship to the wedding alter. How many marriages with children are formed like this that are now gone?
    The number of woman that suffer and are afraid to pass it to a child . Add all these up.. This fear could reduce female birth rates from 1.7 to 1.5!

    It would be easier to find a mate in a country where half the people have it and nobody cares / where doctors tell you that you don’t have it after a single negative swab test, than in a developed country, some of which have laws about having sex with an unknowing partner while carrying this disease. So one gets punished for testing for knowing ! It is a disease about which it can be said that if everyone has it then nobody has it.

  3. Hi Dr. Bill,
    I was excited to read your enthusiasm and conviction about a successful approach for HSV-2 vaccine, but when I searched Pubmed for your research, the related titles in the margin were contradictory. There were two (by the same author) which described how for 50 years, attenuated live/dead virus vaccines had failed and dna vaccines were the way to go. I apologize if you’re addressed this elsewhere, but can you explain the discrepancy of earlier live/killed vaccine failures and your success?
    -Long time sufferer

    • Hi Long-Time Sufferer,

      You wrote……….

      “Hi Dr. Bill, I was excited to read your enthusiasm and conviction about a successful approach for HSV-2 vaccine, but when I searched Pubmed for your research, the related titles in the margin were contradictory. There were two (by the same author) which described how for 50 years, attenuated live/dead virus vaccines had failed and dna vaccines were the way to go. I apologize if you’re addressed this elsewhere, but can you explain the discrepancy of earlier live/killed vaccine failures and your success?
      Thanks, -Long time sufferer”
      I reply as follows……..

      What I am saying in this blog is that based on 20+ years of experience studying herpes immunology and herpes simplex virus in animal models, it is my expert opinion that a HSV-2 vaccine is infinitely feasible, but the “HSV-2 vaccine field” has effectively been backing the wrong horse for 30 years by virtue of investing >99% of money put towards HSV-2 vaccines into approaches such as Glaxo Smith Kline’s Herpevac vaccine.

      To be clear, this is my opinion and is not necessarily representative of the views of the hundreds of individual scientists who have contributed to the “HSV-2 vaccine field” over the past 30 years. My explanation for the “discrepancy” you cite is that any author who states that a “live-attenuated HSV-2 vaccine” has been developed and meaningfully tested is in my estimation either misinformed or is not telling the whole truth. A traditional “live-attenuated HSV-2 vaccine” (that is replication-competent) has not been injected into a single person in the United States in a clinical trial ever. Period. End of sentence.

      If that is the landscape, and we have never actually tested a live-attenuated HSV-2 vaccine in a U.S. clinical trial, then clearly we are lacking sufficient evidence to offer the judgment that a live HSV-2 vaccine would not work.

      I note that you refer in your query to an “attenuated live/dead virus vaccine” as though it is a single entity. From a scientific standpoint, this is sort of like asking, “Well, some car experts have offered the opinions that Lamborghinis/Model T’s don’t go very fast. What do you think?”

      What I think is that Lamborghinis are very fast cars, and Model T’s are not and that they should never be separated by a hyphen as though they are remotely similar. Likewise, I think the “HSV-2 vaccine field” is filled with a lot of individuals who are either (1) uninformed or (2) have simply lost sight of the simple, self-evident fact that live-attenuated viruses make fabulous vaccines because they faithfully recapitulate “the look” of the infectious agents we are trying to teach the body to recognize and fight off before they may cause disease……this is how we previously or currently prevented smallpox, yellow fever, poliomyelitis, mumps, measles, rubella, chickenpox, shingles, and rotavirus-induced diarrhea. This is a tried-and-true approach and works well, but the most recent generation of vaccine scientists have bought into a belief system that “live-attenuated virus vaccine” = “killed virus vaccine” = “viral protein subunit vaccine.” That is, any and all of these approaches are interchangeable, and any one may be used to prevent HSV-2 genital herpes.

      From a non-scientific standpoint, my position is that such opinions either reflect the fact that the person offering them is (1) uninformed or (2) simply not the sharpest tack in the box. From a more scientific standpoint, my position is that none of the experimental evidence gathered over the past 50 years supports this position; live-attenuated vaccines consistently outperform other approaches such as “killed vaccines” for theoretical reasons that should be self-evident to any microbiologist / immunologist who really thinks through the details.

      A sampling of the evidence and arguments to support my position that “a live-attenuated HSV-2 vaccine” offers superior protection relative to other HSV-2 vaccine approaches may be found here:
      1. http://www.ncbi.nlm.nih.gov/pubmed/24837838
      2. http://www.ncbi.nlm.nih.gov/pubmed/23755244
      3. http://www.ncbi.nlm.nih.gov/pubmed/21412438
      4. http://www.ncbi.nlm.nih.gov/pubmed/23843891

      Long-time sufferer, if there was consensus that what I am saying is true, and the entire HSV-2 vaccine field shared in my thought process, then we would already have a live-attenuated HSV-2 vaccine in a U.S. clinical trial. We do have the ACAM-529 vaccine trial, which is a step in the right direction, but which is not truly a “live-attenuated vaccine” because ACAM-529 is a HSV-2 virus that cannot replicate in a vaccine recipient. All of the successful “live-attenuated virus” vaccines I cite above are capable of undergoing viral replication in vaccine recipients, and it is more likely than not that “viral replication” will be required to obtain an optimal HSV-2 vaccine. At a minimum, the scientific community should be considering “Plan B” in case the ACAM-529 vaccine proves to be over-attenuated and incapable of eliciting sustained protection against HSV-2 genital herpes.

      Finally, please allow me to point out that in science, it is quite common for a “great discovery” to emanate from thinking that contradicts the conventional wisdom of the day. A few examples are……

      1) For thousands of years, it was generally believed that the Earth was flat and lay at the center of the universe. The people that offered opinions to the contrary were not greeted kindly in their day….at least one was burned at the stake and the others were viewed as heretics as recently as 400 or 500 years ago.

      2) Heavier-than-air flight was generally viewed as impossible until the Wright Brothers developed the proper wing engineering / shape to make it happen in the early 1900s.

      3) The atom was known to be the smallest / indivisible unit and this assumption was a cornerstone of physics and chemistry until Albert Einstein and other scientists in the late 19th century / early 20th century developed unorthodox views that perhaps atoms could be split to release their energy. The development of atomic bombs and nuclear energy only came about because of this new way of thinking.

      What I am getting at in this long-winded response is that new scientific discoveries and paradigms generally emerge from areas of scientific debate, not consensus. The viewpoint I am offering on this blog that a live-attenuated HSV-2 vaccine is (1) infinitely feasible and (2) could be used to immediately start protecting people against HSV-2 genital herpes. While I am aware that this opinion does not reflect the current consensus of the “HSV-2 vaccine field,” nonetheless the available evidence firmly supports the central claims that (1) a traditional live-attenuated HSV-2 vaccine (that is replication-competent) can be made uber-safe and (2) would be ~100-fold more effective in preventing genital herpes than what we have been advancing to U.S. clinical trials for the past 25 years.

      So, no, my opinion does not reflect the consensus beliefs of my colleagues, but rather reflects our best possible approximation of “nature’s truth,” as defined by the available experimental evidence.

      – Bill H.

  4. Thanks Bill. I would still much prefer if rather than a vaccine there might exist some way the body could get rid of the foreign virus DNA within the cells. I don’t know if there is any possible way the body could achieve this? For example I think I read somewhere that there are even cellular defence mechanisms but the viral DNA is able to combat them. I don’t know if by shutting down the HSV DNA’s combat ability it may be possible the cellular defence mechanisms could eliminate it and the infected nerve cell could remain alive?

    Regarding less than 100% effectiveness I think Dr Frazer ( former “Australian of the Year” for work on developing a HPV vaccine which i’m not sure is 100% effective itself ) who is running the Corridon HSV vaccine research here in Australia was once talking about developing a HIV vaccine that would be 50% effective. However like you said I don’t see the point in developing vaccines that might protect you a little bit or make your suffering just a little bit less……

    I guess with the live attenuated virus people may be scared that the attenuation may not work correctly and the virus may actually be fully functional (or even worse) and create a permanent infection. I don’t know if it might help to prove with animal models which have received the attenuated virus that they have not acquired a permanent infection? Have the FDA made any suggestions as to how your vaccine could progress to human trials? Also if you set up a company on the stockmarket for raising funds I would like to know so I could invest in it based on the share price jump in the company set up for the Corridon fund raising ;-)

    I hope there is a cure for HSV soon – many people seem to think it’s not an issue but I think it’s a horrific disease and it depresses me every day. Apparently many people have little or no symptoms ( eg I heard somewhere that people of asian descent have better defence against the virus ) but I get sick with it

  5. Dear Bill, I was wondering if rather than developing a vaccine, anybody might be working on a cure? However I guess a cure would be far less lucrative. For example here in Australia they are completing stage 1 human trials for the Corridon herpes vaccine and shares in the company that is funding the research have jumped from 1 cent to 17 cents in a few months on the basis of a few press releases so I guess some people are already making lots of money!

    I almost feel like I don’t mind the failure of herpes vaccines to date because I would rather people were working on a cure – to me it seems like the vaccines cannot guarantee you won’t be permanently infected by herpes as there is a chance it could slip past your immune response so their main purpose is therapeutic with reduced outbreaks

    Does a cure seem a possibility to you? Is it possible the virus could be destroyed in the nerve cells which carry it? Or is it possible the nerve cells which carry it can be killed? ( I don’t know if its possible for nerve cells to die and grow back. Sorry about my extreme scientific ignorance!

    • Dear Ben,

      Yes, I believe that a HSV-2 vaccine that actually works would effectively be a cure.

      We know that a live HSV-2 vaccine would work at least 100 times better than the Agenus HerpV vaccine, based on side-by-side animal testing of (1) whole viral vaccines versus (2) HSV-2 subunit vaccines. Several studies, including one from my lab, have repeatedly established this simple and important point over the past 5 years.

      The problem lies at the level of human clinical trials. Although HSV-2 subunit vaccines have a very limited capacity to succeed as vaccines, more than 15,000 human subjects have been enrolled in U.S. clinical trials of HSV-2 subunit vaccine approaches. The real number of human subjects screened for HSV-2 subunit vaccine trials has been more than 40,000 people. That is an awful lot of time and money invested in one particular HSV-2 vaccine strategy.

      Now, as I was saying, whole / live HSV-2 viral vaccines are a completely different strategy that works 100 times better than subunit vaccines. If HSV-2 was a person and a HSV-2 subunit vaccine was a cat, what I would be saying is that it is not realistic to expect that a 10 kg cat sitting in HSV-2’s lap is going to be adequate to pin this virus down. However, if we had a vaccine that was 100 times more effective against HSV-2, then that would be like saying, “Why don’t we try parking a 1,000 kg car on HSV-2’s chest and seeing if that slows this thing down a bit.” A 100-fold increase in effectiveness is huge.

      So then the question becomes, “How do whole / live HSV-2 viral vaccines perform in U.S. Clinical Trials?”

      Ben, that’s a great question. My answer is……we don’t know, because we have not injected a single human subject in a U.S. Clinical Trial of a whole / live HSV-2 vaccine at any point in the past 40 years. Rumor has it in the world of science that it is very hard to discover the answer to questions that we never ask and/or never test.

      Yes, HSV-2 genital herpes can be cured, and an effective HSV-2 vaccine is the most logical / practical way to achieve this goal. However, we need to start testing HSV-2 vaccines that work as best as can possibly be expected, as opposed to focusing on ideas like the HerpV vaccine are folly, and probably elicit about 1/1000th of the protective immunity against HSV-2 that is possible.

      Runners can’t win races when you bind their legs with rope, and vaccine scientists cannot cure HSV-2 genital herpes when we let the FDA run the show and eliminate live / whole viral HSV-2 vaccines as an option because they are “too dangerous.” The flaw in this reasoning is that about 10 to 20 million people per year are in the same boat as “Just diagnosed” (who posted a comment on the blog this afternoon) and continue to contract a disease-causing HSV-2 infection that they are stuck with for life. To sit around and talk about the HerpV vaccine and a “15% reduction in HSV-2 shedding” is to continue wasting valuable time. Every day we waste talking about the HerpV vaccine (that does not work) translates into another day that 40,000 people worldwide will contract HSV-2 genital herpes with no hope for either a (1) preventative HSV-2 vaccine or (2) a real therapeutic HSV-2 vaccine.

      We deployed a whole / live herpesviral vaccine in 1994 or 1995 in the United States to prevent chickenpox, and today in 2013 I am only a few years away from lecturing to a class of medical students who will look at me like a relic for even suggesting they should waste time learning about a disease of the past like “chickenpox;” I already get this look from most U.S. medical students when I teach them about smallpox and poliomyelitis. Chickenpox is in the process of becoming a vaccine-preventable disease of the past because nearly 20 years ago, the U.S. made a concrete step in the right direction of deploying a whole / live varicella-zoster viral vaccine that actually works. It is infinitely possible to achieve the same type of vaccine-mediated victory over HSV-2 genital herpes, but to achieve this goal we need to shift our focus from HerpV and such “molecular HSV-2 vaccines” that sound fancy but which are hopelessly ineffective. I believe that our time and money would be better invested in bringing HSV-2 vaccines that actually work to human clinical trials.

      As I indicated in my recent blog post, the HSV-2 ACAM-529 (http://www.niaid.nih.gov/news/newsreleases/2013/Pages/HSV11-8-13.aspx) is a concrete step in the right direction. It’s about bloody time that the NIH put some money behind a HSV-2 vaccine that actually has some scientific substance, and is not just another sales pitch!

      – Bill H.

      • Bill – I just noticed on this particular post you wrote HSV2 can be cured and an effective HSV2 vaccine is the most logical and practical way to achieve this goal. That is the answer people are hoping for.

        Please hurry and find investors to fund a clinical trial to make this a reality!

  6. Good questions Bill. The man does not respond to valtrex or famvir. He has been on both episodically and for supression and neither has helped with the duration or stop the legions from coming. In addition to the basic viral culture (that has a higher false negative rate), he has also done viral PCR swabs (that are more accurate). This is in addition to all the serology tests. It seems the viral culture could be negative a few times but not time after time after time, especially when the man presents the doctor with a legion on his lip or genital and they squeeze the weaping fluid and scape the sore within 1-2 days of the legion being present on the skin. It just doesn’t make sense. As I said this case has caught the attention of the researchers using Deep Sequencing ViroChip and they have agreed to take it on if the medical provider can work with them to send a sample and it is approved through their IRB. However, as an expert in the field the man is looking for any other thoughts you may have.

  7. One more note the man asked me to include:

    He describes that nerve pain comes when the outbreaks happen in the genital area and burning in the tailbone. In fact, one doctor diagnosed him with “sciatica” because when the outbreaks come he gets pain radiating down his sciatic nerve on the right side of his body. The Drug Lyrica helps with the nerve pain as well as narcotic painkillers. None of the pain occurs until the outbreaks come. It seems the virus is living in the nerves.

    • Hi JR,

      Forgive me for asking the obvious, but are these symptoms alleviated at all by valtrex? One more thing….has anyone ever performed PCR looking for HSV DNA in the lesions? If the disease is driven by herpes simplex virus, then the viral DNA should be easy to detect in these lesions.

      – Bill H.

  8. Thank you Dr. Halford. Other researchers and doctors are also suprised with the presentation of the various body locations. Please note they do not all occur at once but those are various areas where the male has had the blisters. Most typical are herpes whitlow looking presentation, and herpetic presentation on the outer lip and genitals. The main reasons that point medical providers to believe this is a virus are the following:

    1) The fact that the same virus has actually spread to a family member and the blisters look the same and are following the same cycle. The triggers are even similar.
    2) The virus started 7-10 days after intercourse with a HSV-1 infected female. Note that the female actually had a blister on the corner of her lip during the encounter. This was noticed in the morning by the male. She admitted she gets cold sores from time to time and then had a confirmatory HSV-1/2 blood test showing positive antibodies for HSV-1. I wonder if the virus was transmitted to the male and somehow the code of the virus radically altered so that it misses testing biomarkers and does not respond to antivirals.
    2) The original punch biopsy came back as “herpes simplex” but it wasn’t until the dermatologist questioned the result and asked for a HSV 1/2 typing that the lab came back with a completely different diagnosis– Ucler with Necrotic Keratinocytes. If the case is so complex they have to discuss it twice in an interdepartmental meeting it tells me it definitely is suspicious.
    3) The virus reoccurs weekly or monthly (depending on what is happening in the patients life) with the same exact triggers as Herpes Simplex. The blisters are red, filled with a small amount of clear fluid, then crust, and heal.

    Please note Bechets has been ruled out due to locations of the blister. In addition, the male thought it might be celiac disease and the blisters were herpetiformis dermatitis due to ingestion of gluten. However, the male has now been Gluten free for 2 years and this hasn’t caused changes in the recurring virus.

    The male is in otherwise good health with all CBC and other lab tests all normal.

    Thank you again! The community really values your opinion and I know this male is hoping at least someone will have answers or next steps.

  9. Dr. Halford,
    Thank you so much for posting this blog. It is very popular among the Herpes Support Community. I know you aren’t a medical doctor, but I am hoping you can help one of our Herpes Support Community members who has been searching for answers for an unknown Human Herpes like virus for nearly 6 years. I am seeing if you can provide a general opinion or ideas for next steps after reading the full case. I present a man’s suspicious case below from our Community.

    Description: Male, 20s, had sexual intercourse with a female who tested positive for HSV-1 (no known other viruses). Male started to present with blisters on the lips within 7-10 days after intercourse; however over several years the blisters spread to the fingers, hands, feet, genitals, and sometimes even the knee. These blisters contain clear fluid and are painful, red, and itchy. They resolve themselves within 4-7 days depending on the location. Typically they present themselves in the form of 1 or a few blisters. The blisters always heal and the skin returns to normal. The virus is recurring and comes out from various triggers when the immune system is weakened (lots of sun, alcohol, sexual relations, high stress, not getting enough sleep, sugary foods). Doctors have stated that the virus looks and behaves just like Herpes Simplex. The male has documented pictures of the blisters from over the years.

    Testing: HSV 1 / 2 IGG and IGM at least 30 times, 1 University of Washington Western Blot, at least 20 HIV tests, at least 20 Viral Cultures (On mouth, feet, and genitals) for HSV 1 /2 and Zoster. In addition he has been tested for other STDs such as such as Syphilis. Nothing has turned positive and this male continues to seek answer to a problem he cannot fix. He has consulted primary care doctors, infectious disease specialists, dermatologists, immunologists, and prominent herpes researchers. The MOST suspicious test came in the form of a biopsy sample from the lower back. The lab first returned a diagnosis of Herpes Simplex BUT when the dermatologist went back to ask the lab if it was HSV 1 or 2—the lab retracted its original diagnosis and stated “Ulcer with Necrotic Keratinocytes.” The notes state “There is an area of epithelial loss with underlying vessels and inflammatory infiltrate. Histological features are suspicious for herpes virus infection. Immunohistochemical studies were performed to further evaluate/type the viral changes. The lesion was negative for HSV-1 and HSV-2.” In addition, the case was so complex it caused the lab to have an interdepartmental meeting to make a diagnosis. This is very suspicious! My thought from reading peer reviewed medical literature is that the virus could be TK deficient or the known Herpes 1 / 2 tests do not test for the markers for this particular virus. In fact, this could be a new novel Herpes virus.
    What he has done to help: SPF 75 sunblock, completely eliminated alcohol, completely altered diet—however given his stressful lifestyle/job he is still prone to occasional outbreaks. He has tried both Famvir and Valtrex both for occasional outbreaks and suppressive therapy over the years and he does not respond to either medicine. In short he has no weapon against the outbreaks.

    Spreading Virus: The male has not spread this virus to any sexual partners; however he has spread it to a family member from sharing food utensils. The family member now has the same blisters on the mouth, hands, and feet. The family member gets outbreaks when they are run down, stressed or too much sun. The family member was also tested for HSV 1 / 2 twice and the results were negative.

    Latest Doctor Recommendations: The latest recommendations are for this male to seek services from a Deep Sequencing Lab such as UCSF (Chiu Lab). At this point this male really wants an answer to this problem and a diagnosis more than anything. However, this could be extremely costly so he would like to know if other researchers or doctors have any other possible opinions. The virus shows no signs of slowing down.

    Can you please offer any thoughts to this case? I know this male would gladly donate to any lab that could provide him some useful advice into his case. Nearly 6 years of searching, reading, and doctor after doctor have been very rough for this individual. Thank you again for helping someone from our Herpes Support Community. We really appreciate you and your research.

    • Dear JR,

      The short answer is yes, I will consider, but this is obviously a pretty complex case. I don’t know that I can provide a slam dunk answer on this one, but let me chew on the great details that you have provided and see if I can least recommend some possibilities. Based on what you have described, this general pattern of presentation does not strike me as herpes simplex virus. The fact that this person’s female sex partner was HSV-1 positive might be a red herring in this case. Also, I note that HSV-1 in particular (and HSV-2 less so) really likes to move up and down nerve fibers such that the viral infection rarely expands its distribution beyond the initial site of infection. While I have certainly heard of a cold sore expanding its distribution to involve more of the face and inside of the mouth, I cannot say that I have ever heard of HSV-1 (or HSV-2) affecting the lips, fingers, feet, genitals, and knee in a single person.

      Let me give this one some thought.

      – Bill H.

  10. Dr.Halford,
    Thank you very much for developing this blog and posting answers to questions regarding Herpes Simplex. Although tons of research is done for HSV-2, I strongly feel as those with frequent recurring HSV-1 (Oral/and or Genital) that don’t respond to Valtrex/Famvir are left out in the cold. I thought that the AIC-316 trial would offer hope to that group but the trial was terminated. My questions will deal with 2 topics: Chimerix CMX001 and ACAM-529.

    Chimerix CMX001
    I am closely watching Chimerix CMX001 as it has a different mode of action from Valtrex/Famvir and does not depend on Viral TK. Therefore, it is possible that CMX0001 (prodrug Cidofovir) could work well for HSV sufferers that don’t respond to Valtrex/Famvir. In fact, it is well documented in peer reviewed scientific research that Cidofovir is used with success as a last resort for people resistant to Valtrex/Famvir (One example: http://www.ncbi.nlm.nih.gov/pubmed/12100196). Of course, Cidofovir is very risky on the liver but Chimerix will change this with the CMX0001 successful safety profile.
    Although Chimerix isn’t being studied specifically for Herpes Simplex, they claim the drug will work in all DsDNA viruses and have successful per-clinical studies on Herpes Simplex (http://ir.chimerix.com/releasedetail.cfm?ReleaseID=752312). In addition they claim to have data from their Expanded Access Program for Serious and Life Threatening Viruses that CMX001 is working well with various Herpes Viruses.

    My question: What is your view of CMX0001 to provide therapeutic benefit for those with HSV1 or 2 that are resistant to Valtrex/Famvir? Is there reason to be hopeful? This drug would initially be prescribed for other viruses but it will be possible to obtain the drug off label for Herpes Simplex. The drug is already moving into Phase 3 trials and it appears the drug might be able to significantly reduce or completely stop herpes outbreaks as long as one continues to take the drug.

    The NIH is now starting the ACAM-529 trial (NIH trial) with 3 groups. The 3 groups will be (a) subjects who have been infected with HSV-1 and HSV-2 in the past (HSV-1+/HSV-2+), (b) subjects who have been infected only with HSV-1 (HSV-1+/HSV-2-), and (c) subjects who have not been infected with HSV-1 or HSV-2 (HSV 1-/HSV-2-). Vaccine or placebo will be administered on Day 0 and approximately 1 month and 6 months after enrollment
    My questions are the following:
    1) For groups A and B above (already infected), is it possible the Vaccine will serve as a therapeutic vaccine drastically reducing outbreaks for HSV-1 and/or HSV-1 and 2? The scenario would be if you only had recurring HSV-1 that it could slow down or stop those outbreaks and protect you against HSV-2 or vice versa. I am wondering if this is possible and if the trial would be of benefit to someone with recurring HSV-1 (hoping to slow it down).
    2) If you get a Vaccine with a replication deficient HSV strain and you don’t have HSV-2 (only HSV-1) would that mean you would show up on HSV antibody tests as positive for HSV-2?

    Based on your research you have stated “There is some overlap between the antigens / epitopes of HSV-1 and HSV-2.” and “I would predict that a safe and effective HSV-2 vaccine would be sufficient to cover a person’s risk of acquiring HSV-1 or HSV-2 because HSV-1 is a much less aggressive (less virulent) virus. Even though an effective HSV-2 vaccine would be only partially protective against HSV-1, this would probably still confer enough protection against HSV-1 to do the trick.” I am wondering how this would translate to therapeutic benefits.

    Thank you very much and I look forward to your response.

    • Hi Jarrett,

      With regards to your post of Sept 7, could you please re-state a single question? I feel like you are commenting on a half-dozen different issues in your post, and then asking a primary question with many secondary spin-off questions.

      Please pick what you feel is the singlemost pressing question, ask in a new post, and I will address that one question. You can ask the other questions later. I just think that it is easier for other readers (and for me), if we restrict our Q & A to one issue at a time.

      Thanks for the post. I hope to provide you with a more rapid answer to your next post.

      Bill H.

  11. Hi Bill,

    My name is Deb and I am San Francisco Bay Area-based artist who makes science themed t-shirts and paper screen prints. My husband is a microbiologist who got his PhD in Infectious Diseases & Immunity at Cal and worked in the Glaunsinger Lab on KSHV in grad school. I have a really awesome herpesvirus t-shirt on my website, and I am looking to just get my work out there and reach out to scientists!

    My website is http://screenology.net if you’d like to check it out, or feature it in a post or anything. Thanks for taking the time to read this comment. :-)


  12. Dear Bill,

    Of course, I was in no way suggesting anything untoward or illegal. I’m going to start examining this to see if there is a framework within the US that would allow such a trial, or perhaps a jurisdiction elsewhere which would better serve. It’s great to hear that you’re potentially interested should a completely legal, but also financially realistic, pathway be found to some sort of preliminary trial attempting to show therapeutic effects. I do believe, with the difficulty you and others have had in overcoming the objections to a live-attenuated prophylactic vaccine, that a therapeutic effort could be an important alternative. I’ll keep in touch if it looks like a find a promising methodology. I am also able and willing to invest into such an effort.

  13. Dear Bill,

    I posted a similar message in an older thread on this blog, but felt posting it here may enhance the possibility you are able to view it.

    My thought is this: if we could provide data to the NIH that a vaccine had a therapeutic effect, especially if it could be shown that such a vaccine could reduce viral shedding, then wouldn’t the NIH lean toward funding further research on such a vaccine?

    Simple math: less shedding would lead to less transmission. Therefore a vaccine which reduced shedding, and which was ONLY PROVIDED TO ALREADY INFECTED INDIVIDUALS, would have a society-wide benefit through transmission reduction. Yet there should be no concern about live-attenuated vaccines infecting the uninfected, because they would not be given to the uninfected in the first place. Seems like there should be no objections to this approach.

    So why not start gathering the data? Lets organize a group of volunteers, people who are already infected, and inoculate them with live-attenuated HSV-2 ICP0- mutant vaccine, and then measure the therapeutic impact. I will personally volunteer and organize however many volunteers you would require.

    • Hi JD,

      You wrote, “So why not start gathering the data [from a human clinical trial]?”

      Because there are very strict rules in place about experimental testing in human subjects, and this is common knowledge amongst universities, hospitals, and the pharmaceutical industry. I like my job, the salary that comes with it, and the ability to help feed and clothe my family. While I am very happy to help move a HSV-2 vaccine towards human clinical trials, I am constrained by the rules of the law and must operate within that framework.

      If there is a legal mechanism within the U.S. or abroad to start a human clinical trial of my lab’s live-attenuated HSV-2 ICP0- mutant vaccine, count me in!

      – Bill H.

  14. Thank you bill,

    Thank you for your reply. No worries at all, whenever you have time would be greatly appreciated.


  15. Hello Doctor,

    Once again great work with all that you are doing. Please forgive the clumsy medical terminology below. ( I’m an engineer not a microbiologist or md).

    I stumbled across your site while researching a few points regarding Cutaneous wild type HSV2 infection (forearm) ( capri ulnaris and radial nerve ) and exogenous reinfection possibilities. Many experts have referred to such acting as a “virtual vaccine” and this seems to be the general consensus. I believe this thinking subscribes to the methodology that you have applied to your research and work, i.e an attenuated vaccine. There seem to be a few articles that show the possibility of super infection from various strains of wild type HSV2. Can the same be said for re exposure of the same strain and type of HSV or will this previous inoculation infer complete immunity in your opinion? Also regarding wild type infection how long will this immunity last in your opinion Doctor?
    I would really appreciate any feedback you could give me, be it via this blog or even a direct email as it had been very difficult to find an expert on this topic. Also as mentioned before I would like the opportunity to discuss your vaccine with you further in terms of possibly progressing to further development so please feel free to contact me via email.

    Regards and many thanks

    Tony Stark

    • Dear Tony,

      Thank you for your comments / queries.

      Please forgive the delay in my response. I am getting there and wish to address this post and your earlier post in earnest, but I am simply short on spare time at the moment. I will get back to you, but this may not happen until this weekend after I take care of a few other matters.

      With best regards,
      Bill H.

    • Hi Tony,

      I have (finally) had a chance to review your case via the link you provided below and which I copy-and-paste here for the convenience of other readers (http://www.medhelp.org/posts/STDs/HSV2-Upper-Back/show/1935953). In essence, your questions boil down to:

      1. Can you really acquire a HSV-2 infection between the shoulder blades on your back?; and if so, then…..
      2. Does a HSV-2 infection between the shoulder blades confer protection against a secondary HSV-2 infection of your genital region?; and
      3. Can a HSV-2 infection acquired between the shoulder blades be transmitted via the genital route?

      Tony, I can provide an unambiguous answer to Question 1 and a slightly softer (squishier) answer to Question 2. With regard to Question 3, I can give you my best educated guess, but you really are wandering into the type of territory that compels me to say, “I am just a researcher and not a physician;” “This is an educated guess that should not be construed as a legally binding professional opinion;” disclaimer, CYA language, more disclaimers, etc. Long story short, I can help you understand the biology of how HSV-2 works so that you can make appropriate choices, but when you in essence ask a MD or a professor “Can I be confident that I won’t transmit my HSV-2 infection to someone else?,” this is such a loaded question that it really becomes tricky for me to give a concrete answer to you (and potentially scores of other people in the same situation who read this blog) without exposing myself to some legal liability. Having established all the caveats and disclaimers, I proceed to answer your questions.

      1. Can you really acquire a HSV-2 infection between the shoulder blades on your back?

      Absolutely. HSV-1 and HSV-2 can both infect any surface on the body, but the issue is that the intact outer layers of our body (e.g., skin or mucosal epithelium) are such a formidable barrier that infectious HSV-2 (or HSV-1) virions rarely succeed in making the trip across the skin and infecting the cells BENEATH THIS OUTER LAYER that can actually support HSV-2 replication. If you look at Figure 1 in the following 2004 publication from my lab (http://jvi.asm.org/content/78/18/10086.full.pdf+html) what you will see is a very simple experiment that powerfully illustrates this point. In this experiment, I inoculated 3 groups of mice with the exact same 100,000 pfu dose of HSV-1 on their corneas….that dose of virus is probably 100 times higher than the typical person is exposed to when they first contract a HSV-1 infection. In this case, the HSV-1 virus used in the test was genetically engineered to express a green jellyfish protein called “green fluorescent protein,” which allows you to “see” the HSV-1 infected cells at 24 hours post-exposure to this very high dose of infectious HSV-1. What the data shows is that virtually 100% of mice whose corneas had an intact outer layer completely repelled (held back) the infectious HSV-1 and a productive infection did not result. In contrast, mice whose corneas were scratched lightly or vigorously just prior to infection support 100 to 10,000 times higher levels of HSV-1 replication at 24 hours, and thus the cells in their cornea that are supporting HSV-1 replication are visibly “green.” Take-home message: all the cells just under the surface of the epithelium in your eyes, mouth, nose, genital tract, or skin covering your entire body can support HSV-1 or HSV-2 replication. However, statistically speaking, the sites that are broken (chapped or abraded) most often in the natural setting are the lips (chapped lips) or the genitals (which are abraded during sex…..particularly in newer couples who tend to have a few repeat performances per night).

      Coming to your case, exposure to infectious HSV-2 was key, but probably a few minutes of grinding and/or an abrasion on your back was the culprit that let HSV-2 gain access to the critical cells BENEATH THE OUTER LAYER OF DEAD CELLS / KERATIN THAT IS “THE SKIN.”

      Other more common examples of such infections are “herpetic whitlow” that dentists used to get all the time in their fingertips in the “pre-gloves” era of dentistry and “herpes gladitorium.”…..wrestlers bite each other when they wrestle, and sometimes there is a little something extra in the saliva.


      2. Question 1 was easy. Question 2 is a bit harder in terms of what has been said in the literature, on the internet, etc. The simple fact-of-the-matter is that your impression of how the system works is well supported by all of the experimental evidence. That is, what the data says is that the first time HSV-1 or HSV-2 have free reign to colonize a new site in your body is (1) during the primary infection and (2) prior to the clonal expansion of B- and T-lymphocytes specific for the virus. In practical terms, what this means is that HSV-1 or HSV-2 can spread quite far during the first week of a primary infection, but the ease with which the virus spreads decreases dramatically thereafter. In general terms, this resistance to HSV-1 or HSV-2 infection elsewhere in the body should be life-long provided that the immune response to HSV-2 (or HSV-1) is maintained over time.

      So, I would say that if you had a primary HSV-2 infection of the back (between the shoulder blades), then you are indeed at a dramatically decreased risk for acquiring a genital HSV-2 infection relative to before when you were immunologically naive (and thus had no activated HSV-2 specific lymphocytes and no anti-HSV-2 antibodies). While you might be exposed to HSV-2 in the anogenital area, your body should have a heightened ability to combat that infection and prevent it from reaching your dorsal root ganglia en masse and establishing an infection that is capable of reactivation and/or producing visible symptoms.

      Yes, you are correct that this is precisely the same principle than an effective HSV-2 vaccine relies upon to confer protection. However, I would not recommend “pony rides” as a universal mechanism to vaccinate the human population against HSV-2 genital herpes. There are safer and more conventional means to achieve this goal, such as a live-attenuated HSV-2 vaccine. However, in principle, your assumptions about how immunity to viral infections are gained is correct, and a primary HSV-2 infection at one site should leave the rest of the body highly resistant to HSV-2 infection at another site.


      3. By and large, when a primary HSV-2 infection is established in the back between the shoulder blades, the latent HSV-2 infection that is established will be found in the dorsal root ganglia coming off of the upper half of the vertebrae…..an actual MD who is more familiar with human anatomy would likely tell you that the dorsal root ganglia coming off of segments T4, T5, and T6 (or something like that) are where the latent HSV-2 virus lives in your body. The following link takes you to a map of the vertebral segments (http://www.google.com/imgres?imgurl=http://johnhawks.net/graphics/vertebral_column_labeled_colored_2010.png&imgrefurl=http://johnhawks.net/explainer/laboratory/types-of-vertebrae&h=867&w=600&sz=60&tbnid=8oJQMQfnIb2F6M:&tbnh=90&tbnw=62&zoom=1&usg=__QhSAOiKc1i8B6Q-bmfWGF7I-zLo=&docid=sjocV5dLyCnwDM&sa=X&ei=3koWUuy8F42A2AXDpICYDg&ved=0CD4Q9QEwBA&dur=92). The relevant thing to note is that the latent HSV-2 DNA that lives in the dorsal root ganglia of people with genital herpes lives in the ganglia coming off the lumbosacral segments of the vertebrae (i.e., the ones towards the bottom of the spine). Thus, when their latent HSV-2 reactivates, the virus re-emerges from the same place it entered…..the anogenital region. In your case, if your HSV-2 infection reactivates, it will go to the same place it entered…..your back. Aside from the distance from your shoulder blades to your groin, the intact skin of the back is not well set up to efficiently help HSV-2 to complete the next step of its life cycle……transmission. That is, HSV-2 is well evolved to spread by the genital route because infectious HSV-2 can much more easily cross the mucosal (soft) epithelium in the vaginal tract of a woman or the urethral tract of a man, and thus asymptomatic transmission of HSV-2 via the genital route is quite common. I doubt asymptomatic shedding of HSV-2 from the back is particularly likely.

      Bottom line: This is not a professional medical opinion, and should not be construed as such, but I generally agree with your interpretation that a HSV-2 infection between the shoulder blades is not going to be as “high risk” for HSV-2 transmission to future sexual partners as a HSV-2 infection of the anogenital region. That said, never say never, and I concur that informed consent is the key. As long a future love interest knows the score that you have been infected with HSV-2, albeit an atypical area, then the two of you can decide how to proceed from there.

      Finally, I am always willing to talk to venture capitalists with a vested interest in a cure for HSV-2! I would suggest a phone call or e-mail if you wish to pursue this line of inquiry further.

      – Bill H.

      • I have had outbreaks only on my lower back, never ever had any sign of it on my genitals…what is the likelihood of transmitting this disease if I receive oral sex or through vaginal sex?

        • Hi Anna,

          I would assume that your odds of transmitting HSV-2 to a sexual partner via vaginal sex are lower because your outbreaks occur on your back. However, I think you know what I am about to say……never say never. You would still pose some risk to a sexual partner, as the ganglia that are sending HSV-2 to your lower back / upper buttocks may also send nerve fibers to your vagina.

          Condoms and antiviral drugs are part of the typical package to further reduce your odds of HSV-2 transmission to a partner, but I cannot tell you that there is no risk……just a lower risk because your vaginal region is not the dominant site of your visible outbreaks.

          – Bill H.

  16. Dr. Halford,
    Though I appreciate it won’t do much for those of us that currently suffer from HSV, now that Dr. Knipe’s vaccine has started clinical trials with the backing of a company with the clout to see it through like Sanofi-Pasteur is that more or less the end of this tragic story? Should we be hopeful for a successful prophylactic vaccine in roughly 10 years?
    If you believe that his vaccine is likely to be successful is ther anything we as the HSV suffering community can do to help make sure it does actually come to market?

    As always thank you for you hard work and support

    • Hi Staying Upbeat,

      What I think we can safely conclude is that the ACAM-529 vaccine (developed by David Knipe and Lynda Morrison) is a huge step in the right direction, and that it is great that this HSV-2 vaccine has been carried through to human clinical trials with the backing of a major pharmaceutical company, Sanofi Pasteur. Moreover, I would suggest that of the potential approaches being taken into clinical trials, I would guess that the ACAM-529 approach is the most viable of the HSV-2 vaccine approaches being discussed.

      Regarding how all this will play out, I would suggest that it is premature to (1) count your chickens before they hatch or (2) assume that a therapeutic HSV-2 vaccine is out of the question.

      Regarding the first point, the ACAM-529 vaccine is a non-replicating viral vaccine. Not once in the 200-year history of vaccines have we successfully eradicated an infectious disease with a non-replicating vaccine; that is, all of our successful live-attenuated viral vaccines actually undergo replication in the vaccine recipient. Thus, at the end of the day, the ACAM-529 vaccine is an experiment, and like all experiments I will be a lot more confident in predicting how it will turn out after I see the results. I wish Dr. Knipe and colleagues the best of luck, and I hope that the ACAM-529 vaccine is sufficient to prevent genital herpes.

      Regarding the second point, I agree that we have historically used vaccines primarily for the purpose of prevention, and thus a prophylactic HSV-2 vaccine should be our end goal. However, I have seen too many reports from too many investigators spanning 50 years of published literature to simply dismiss the possibility that a robust HSV-2 vaccine might be able to work in an “after the fact” fashion as a therapeutic vaccine. A therapeutic HSV-2 vaccine does not have to work, but remains a viable option that I believe we should entertain and experimentally test.

      – Bill H.

  17. Dear Bill,

    1st I wanna thank ppl like you who are working so hard for humanity. God bless always !!!

    Secondly I’m sorry but I need important info which I’m unable to find on net n embarrassed to go to a doc.
    I MIGHT have genital herpes and outbreak on right now ( could be balanitis). So I went to get a blood test and they suggested that if I have an outbreak right now then I should go for igm test , which came out negative. On net I’m getting info that igm should not be done but igg but I suspect I recently got this infection (either herpes or balanitis) so igg will also show negative as antibodies takes months to show in the body.

    Pls clear my confusion, I’m super stressed

    Thanks n wud appreciate you getting me outta this stress.


    • Hi Sameer,

      Please allow me to suggest that there are other websites that are already established, and much better set up to provide information and support for people recently diagnosed with genital herpes. These sites include, but are not limited to:


      If you join these groups, I think you will find the people there are far better equipped to address the many questions you may have.

      – Bill H.

      • Have you thought of creating a Kickstarter campaign to raise funds for clinical trials? Since there are so many millions of people with HSV in the US alone, if only a percentage of them donated you could raise a good chunk of change. How much do you need in order to go into trials?

        All the best.

  18. Dear Bill H,

    Congratulations on the excellent work that you are doing both in the research in developing your vaccine but also in keeping the public informed of the progress and limitations of the research which is currently happening. I was wondering if I could get your expert opinion on an issue in relation to infection outside of the anogenital area.

    This is my case: http://www.medhelp.org/posts/STDs/HSV2-Upper-Back/show/1935953
    I have seen this type of scenario being referred to as virtual immunity and this thinking is also concurrent with your post Live HSV-2 vaccine vs subunit HSV-2 vaccine. Essentially that wild type hsv2 in a different location offers a very, very high level of immunity to reinfection. Yet there seems to be some contradictory evidence in publications such as this article which somewhat questions this. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223069/
    Your insight would be greatly appreciated.

    Also as a side note i saw your correspondence with OTB about the commercialisation of this research and agree wholeheartedly. As a venture capitalist specialising in leading technologies ( hence the name ) I find it fascinating.


    Tony Stark

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