Purpose of the Herpes Vaccine Blog

halford headshot 276x300 Purpose of the Herpes Vaccine Blog

Bill Halford

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.

 

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

 

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67 Responses to “Purpose of the Herpes Vaccine Blog”

  1. William June 16, 2013 at 8:29 pm #

    Amazing work and a great read. How far off are we from having this vaccine to help millions of people around the world?

    This should be put out to the wider public to generate a quicker solution. You should you use a PR firm to get this publicised and the project funded.

  2. jojo June 18, 2013 at 7:22 am #

    Living with Herpes is really hard, especially when you are a single. According to a report from the official Herpes singles dating site Localherpesdating.net, 98% of its members who used to be on a general dating site to find the love and support were rejected by others. That could be the reason that why it is so popular and now has more than 730,000 members and most of them are verified. It also offers 24X7 customer services.

    • JB November 17, 2013 at 7:37 pm #

      Bill how can you allow such obvious spam on your blog? According to a herpes dating site 98% of members were rejected by others? Of course a herpes dating site would spread this type of fear in hopes people read it would pay to join their site.

      I have been a regular at another, free, non dating herpes support website http://www.herpes-coldsores.com for over 4 years and have chatted with thousands of people there and can tell you that most of them have NOT been rejected because they have this virus.

      The key to this is to be educated about this virus. Herpes is just a very common, mostly harmless virus. 90% of adults have it in one form or another. Anyone who has ever had mono, chicken pox or a cold sore has herpes. If this information was widely reported, there would be no stigma.

      I have had this virus for over 25 years and have lived a normal life. I have given the ‘talk’ many times and have NEVER been rejected. I have dated many women and have NEVER passed this along. I have met others who have been married decades and have not passed it along to their spouses.

      I wish you luck in your research, but I hope others realize that this is really no big deal. You can live a normal life with this virus.

      • Bill Halford November 17, 2013 at 11:30 pm #

        Dear JB,

        Thanks for sharing your perspective. You know the saying “beauty is in the eye of the beholder,” well I think you can say something similar about herpes that goes something like “the magnitude of the problems caused by herpes varies wildly from person-to-person.” For some people, it is some occasional skin irritation and discomfort, and is no big deal. I have discussed with other very credible people situations in which they have lived with non-stop outbreaks for more than 5 years, since having to start on immunosuppressive medications. Aside from the severity of the symptoms (which vary wildly), people’s approaches to sexuality, dating, and relationships vary massively as well.

        On one hand, I thank you for expressing the point that people can move on beyond a genital herpes diagnosis and carry on; that is excellent for me to hear, and has to be encouraging to many readers. However, I think it is important to balance that sentiment with the acknowledgement that there are some people with HSV-2 infections who legitimately have a harder time getting around the HSV-2 problem due to the severity of their symptoms and/or the way that HSV-2 impacts them emotionally.

        Thanks for sharing.

        - Bill H.

  3. Kelly June 23, 2013 at 1:18 pm #

    Amazing work and I am so happy that there are scientists like you who are devoting their career to this research. I have been a lifetime sufferer of HSV 1 – oral cold sores. I was wondering if you have any scientific insight as to how soon an HSV 1 vaccine could be created after a successful HSV 2 vaccine is approved and marketed? Do you have any insight into the differences that will need to exist between the two?

    Thanks so much

    • Bill Halford June 27, 2013 at 4:11 am #

      Hi Kelly,

      A safe and effective HSV-1 vaccine is technically very simple, and could be developed any time once we have a template for how to achieve a safe and effective HSV-2 vaccine. At the level of the human population and in the practice of medicine, the HSV-2 virus causes a larger burden of disease and this is the reason companies are most interested in a HSV-2 vaccine. Once we know how to make a good HSV-2 vaccine, it should be very simple to translate this into a HSV-1 vaccine.

      HSV-1 and HSV-2 are simply what are known as two “serotypes” of the same virus. All this means is that in order for HSV-2 to be successful at infecting people who already have the HSV-1 virus (60% of people are infected with HSV-1 by 6 years of age), HSV-2 just slightly modified its 75 proteins so that they are not efficiently recognized by the human immune response (e.g., IgG antibodies and T-cells) to HSV-1. This is not unique to herpes simplex virus. When you hear all the H3N2, H5N1, bird flu, swine flu, etc. stuff on the news about the latest influenza virus epidemic, these are new “serotypes” of influenza virus. Same basic virus, but with slightly modified proteins that allow the new strain to infect you in the winter months even if you have been infected with other serotypes of influenza virus in the past.

      So, HSV-1 vaccine…….should be easily accomplishable, once we first reach an agreement on how to make an effective HSV-2 vaccine.

      - Bill H.

      • Kattie June 27, 2013 at 5:55 pm #

        Hi Bill,

        I really hope that we will have this vaccine soon. As Jojo mentioned, it is very hard to live with this disease. I have no idea how I got it, since my husband is negative and I am very well surprised that I did not affect him which I am happy about it. In another hand, our sex lives have ended not because of him, but because of me. I have outbreaks twice per month since 2003. None of the medications help, actually it makes worse. I also live in a total paranoia of passing it to my young sone, now 8 years old. I am constantly washing my hands and I never ever kiss my son anywhere that is not covered by clothing. I mean I kiss his shoulders or his arms if he has long sleeves on because I read every where that it can be passed on by saliva, so needles to say I have not kissed my husband since I found out I have herpes 1 and 2. I really hope a vaccine will come up some day so people can have some freedom and not live the way I live. This has put a huge stress in my life and I could not imagine going out and trying
        dating anyone if I was out or ever be out in the market of dating again. This is so awful. Thank you Dr. Bill for trying to find help for us.

      • Mark May 27, 2014 at 5:46 pm #

        Just wondering what your take is on Aurx. They have a live weakened virus and seemed to work fairly well. I think they went out of business but they had a successful Phase1/2 study. Any comments on their vaccine as compared to yours?

        Also, Biovax had a live virus vaccine but was purchased by Amgen. Any news on whether or not Amgen will continue this study? How does their approach differ from yours?

        Lastly, not a vaccine, but what happened to NB-001 by Nanobio? Info has been deleted from website, though no results published from Phaase 3 trials. Looked like a good treatment option until something better comes along.

        • 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.

          • 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?

          • 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.

          • 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.

          • 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).

          • 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?

  4. Melanie July 9, 2013 at 8:10 pm #

    I’m interested in a vaccine for uninfected people.

    • Bill Halford July 10, 2013 at 12:22 am #

      Dear Melanie,

      The major focus of HSV-2 vaccine research for the past 30 years has been to develop a preventative HSV-2 vaccine that would protect uninfected people from a later exposure to the HSV-2 virus. This is a highly feasible goal, and is what my first two blog entries (dated June 16th) focused on. You can find more information there.

      - Bill H.

  5. Siegfried July 11, 2013 at 7:00 am #

    Hello Bill,
    It is great that you dedicate your time to find a solution to the problems of millions of people.
    I contracted HSV1 genitally 2 years ago and my life is not the same anymore.
    Constant redness, irritation, pain, sometimes really bad pain (the first year was horrible), blisters only once a year, but very often, basically weekly, light red areas and a constant feeling of inflammation on the glands. Nerve pain in the genital region.
    I never had issues with HSV1 on my lips. It was worse when I was a kid, but now at 46 I just get tiny red stains and they move away soon, no pain. But down there it is just incredible. I did not have much days in last two years when I did not feel anything.

    Sexuality is gone. I have fear to touch my penis, cause this would trigger the next event. Even happens after riding a bike or sitting on a chair, where nerves get pressed.

    Why is it that most of the people dont feel this virus and only 4% as you say have real issues.
    I think part of my immune system is not working properly. No allergies, no other diseases.

    MANY tx for an answer from you.
    I would pay a lot of money to get rid of this incredibly disgusting situation. I mean this.

    kind regards, Siegfried

    • Antonio July 30, 2013 at 11:31 pm #

      Siegfried, you just described exactly what is happening to me . I have HSV-1 genitally 2 years now, and it is horrible. Literally. I have seen the cold sores just once, and they stay like a month. I take acyclovir 800 mg per day, and no more cold sores but my privates are, like u say, red hot all the time. Bill, any suggestions for us living with HSV-1 genitally? thanks.

  6. Praying July 13, 2013 at 2:15 pm #

    Dr. Halford,

    Professor Ian Frazer just started a trial study with 20 healthy people in Australia. He is hopeful vaccine to public in 6 years. He started working on this vaccine in 2008. What are your thoughts on his formula optimization technology?

    How will a vaccine ideally work for someone already infected. They will not have outbreak or they cannot transmit the virus?

    “This is the beginning of an exciting period for our herpes vaccine,” Professor Frazer said.

    “We have seen very encouraging results from animal studies and we expect pivotal data showing that our vaccine, which incorporates our patented optimisation technology, to produce similar immune responses in the clinic.”

    Thank you for all you do!

    Praying!

  7. Praying July 13, 2013 at 6:25 pm #

    Dr. Halford,

    I reviewed your prior notes and put the below my question. I guess if you already have the disease HSV2 a prospective vaccine may boost your immune system, but would not keep neutralize the virus altogether?

    This is your prior notes…

    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.

  8. Hopeful July 15, 2013 at 8:26 am #

    Bill,

    How does this help your research or does it?

    The discovery could lead to a vaccine capable of preventing herpes lesions on people who have already contracted the STI – or in other words, a vaccine that could “clinically cure” an individual of herpes symptoms.

    The newly identified T-cells, called CD8αα+ T-cells, reveal a great deal more information about genital herpes than was initially known.

    “What we found was that (these T-cells) are turned on and making all sorts of antiviral substances,” lead author Dr. Larry Corey, an internationally renowned virologist and president and director of the Fred Hutchinson Cancer Research Center in Seattle, Wash., told FoxNews.com. “When the virus reactivates, they are the first cells in to contain the virus, and we showed they contain it very well. They can contain it before the virus escapes above the skin.”

    Read more: http://www.foxnews.com/health/2013/05/08/vaccine-for-herpes-researchers-discover-immune-cells-that-suppress-hsv-2/#ixzz2Z7GT94B4

    • Bill Halford July 15, 2013 at 1:37 pm #

      Dear Hopeful,

      Perhaps I am being dim, but I personally fail to see how this latest study published by Corey and colleagues has any direct impact on HSV-2 vaccine research.

      A new class of CD8 T-cells has been identified, and now we are more aware of another nuance of the host immune response to HSV-2. However, if this class of CD8 T-cells (alpha, alpha+) is important in 2013, I note that this same class of CD8 T-cells would have also have been important in 1990. Between 1990 and 2012, we have seen six failed human clinical trials of glycoprotein subunit vaccines; I note that Dr. Corey was either the lead author or a co-author on most of those clinical trials. I don’t think that the rate-limiting factor that explains why these glycoprotein subunit vaccines failed was that we had not yet uncovered the role of CD8 alpha,alpha+ T-cells in host control of HSV-2 infection. Rather, glycoprotein subunit vaccines are just lame HSV-2 vaccines…..regardless of whether or not they elicit a robust response from CD8 alpha, alpha+ T-cells.

      I see the recent study of Corey and colleagues as revealing one more nuance of how the human immune system controls HSV-2 infection. While such basic knowledge of herpes immunology is useful and adds another element to the big picture, I don’t think that it fundamentally changes the difference between robust versus anemic HSV-2 vaccines. Rather, the core issues that control which HSV-2 vaccines will be effective relate to (1) HSV-2 vaccine valency (% of HSV-2 antigens included); (2) context of HSV-2 antigen presentation to immune cells (injected proteins vs HSV-2 infected cells); and (3) duration of time over which the human immune system is exposed to HSV-2 antigens (days? weeks? months? years?).

      Bottom line: I suspect that these news releases are 9 parts hype and 1 part substance with regard to how immediately relevant the findings are to yielding a safe and effective HSV-2 vaccine.

      - Bill H.

  9. Ralph July 17, 2013 at 7:17 pm #

    Dear Bill Halford,

    Thank you, And God speed !

  10. mark July 19, 2013 at 3:19 pm #

    Dear Dr. Bill H. thank you for your dedication and effort to develop a vaccine for herpes… i have this virus and i have decided to end my life… but realizing that i have a daughter who’s only 1 year old and a wife who is working abroad and me also in a different country to earn a living and send money back home for my daughter’s milk… it makes me cry and feel so sorry for them… i can take all the burden but knowing that they are at risk and may go hungry once i’m nolonger there for them… i love them so much… i have a dreams for them… i came from a broken family and i always long for a happy family knowing all the pain of not having your parents around you to protect you…. i beg you to please continue your work no matter what obstacle you may face… you are giving us hope and you will save alot of people and their family’s… their dreams…. if ever i will not have the chance for the cure still i will be thankful because the future generation will be safe from this virus… be strong Dr. Bill and thank you for your determination…

    • Bill Halford July 19, 2013 at 6:37 pm #

      Dear Mark, I am sorry to hear that you are in this much pain, and I hope you can work through it. Thank you for sharing and very graphically illustrating what is wrong with FDA policies that hold me back from offering a potential therapeutic vaccine to you. I seriously doubt that my live-attenuated HSV-2 vaccine could possibly make your situation worse, and to the contrary might give you some hope that things could be better. Change is possible, but requires time, persistence, and the will to get out of bed and do it all over again tomorrow. I think that both you and I need to remember this, and make it our personal mantra. I will keep beating on the drum and raising awareness that we can and should do better with our efforts to advance an effective HSV-2 vaccine into clinical practice, and I would ask that you do the same for yourself and your family.

      - Bill H.

    • The HSV Anti-Stigma July 31, 2013 at 11:36 am #

      Mark, I accidentally replied in the wrong place. Please see my reply further below on this page, which was specifically meant for you.

  11. Living life July 22, 2013 at 1:49 am #

    A vaccine would be amazing! As most sufferers will agree it cannot come soon enough. However for those currently suffering here is some advice i have learned over those years about my outbreaks. Stress, lack of sleep, and diet are the biggest triggers.
    Allow time to sleep.
    Try to not stress about the little things in life.
    Diet is tricky, but carefully monitoring of diet and outbreaks will lead you to identify trigger foods.
    For example I love almond milk, however I will have weekly outbreaks if I drink the stuff.

    On top of controlling the “triggers of outbreaks,” a few supplements I have found to be very helpful: red marine algea, lysine, zinc, and echinecia daily will help balance your immune system in between outbreaks.

    My first year, 2003, I had monthly and sometimes bi-monthly outbreaks. With time and controlling my “system,” I now am down to 1 or 2 outbreaks a year….usually very mild lasting a week at longest. While a vaccine is great and much needed, there are many small things sufferers can do today to help!!

    Hope this helps somebody…

  12. tom p July 22, 2013 at 3:33 pm #

    Bill,
    Thank you very much for your dedication and research. I, like many others , would love to see any advancement in a cure/vaccination for HPV 2 and im curious how best to contribute to the cause. I’d love to be able to make donations to research but don’t know where my donation would be best utilized. Clearly I want any money i donate to go solely to hsv2 research. Any recommendations? I’d also like to keep the purpose of donations discreet so as not to write “herpes research” on the check.lol.

  13. The HSV Anti-Stigma July 31, 2013 at 10:01 am #

    Bill, thank you for your work and dedication. This message is directed to Mark, who is considering suicide over HSV. Mark, I want to let you know that the stigma and the condition itself does not deserve that much power over your life. I’m in my 40′s and was diagnosed last year on occurrence of my first outbreak. I have no idea how long I’ve carried the virus, but it first began showing itself during a time of extreme stress in my life. After the initial shock, I began seeking information online. This led me to the discovery of many others suffering from this condition. I found they were living rich, full, complete, and successful lives. They were highly socially active and most importantly, very happy. I realized that many people were living with this condition now, and throughout the course of history. Many people who have done great and incredible things for the world, many who have made discoveries that changed the world, great athletes, actors, musicians, artists, scientists, business people, philanthropists, and every day joes. I decided to NOT let the stigma define me. Once I made that decision the emotional and psychological distress of this condition left me. And with new friends who understood how I felt because they also had been there, I found some of the most honest and fulfilling friendships I’ve ever known. I am happier now than I have ever been. My work life, my family life, my social life, in the end hasn’t changed. Except in that they have become more full. I have deeper appreciation and gratitude for life than ever before. Having said all that, I’m still as interested in a vaccine and the progression of this research as anyone. I fully support this work and look forward to the end result of it. Mark, my point is only that you are not alone. There is no need to let this condition, a highly irritating SKIN condition, be terminal. Put the stigma down, take away its power, support the research and reach out to the amazing community that is available to you. Your life will become more complete than it was before your diagnosis. I can assure you. I’m living proof of it, along with millions of others. This research needs to continue. In the interim, however, there is absolutely no need not reason for despair or loss of life.

    • Bill Halford July 31, 2013 at 11:16 am #

      Dear HSV Anti-Stigma,

      Well said! Thank you for your words, and the thought that went into them.

      - Bill H.

  14. Mark August 2, 2013 at 10:48 am #

    Thank you Bill for your work on this issue. You may contact me if you need any people for your studies.

  15. Tim August 7, 2013 at 3:39 am #

    Dear bill

    Sinaufi pastur has a genetically modified IPC 0 vaccine on the shelf since 2011
    The virus is live attunated but because of the IPC 0 modification the vaccine can’t reproduce…

    This is the best of both worlds…. A full bodied immune response …. Yet 100% safe due to the genetic modification…. Yet acam-529 remains on the shelf

    It cleared phase 1 and phase 2 trials….. And the NIH RECCOMMENDED THAT IT MOVE TO PHASE 3

    So why no phase 3

    I think sinaufi Pasteur bought the company and the vaccine just to shelf it

    • Bill Halford August 7, 2013 at 3:29 pm #

      Hi Tim,

      I believe that earlier / elsewhere in the comments I addressed the conspiracy theory that Sanofi Pasteur bought the ACAM-529 vaccine just to shelve it (with the underlying motivation of making sure that antiviral drug sales are sustained).

      Bottom line: I disagree and have not seen any evidence to support this supposition.

      Moreover, I note that most of the facts you cite are wrong. ACAM-529 is a HSV-2 virus that is replication-defective by virtue of mutations in the UL5 and UL29 genes of HSV-2……hence the “529″ in the name. This HSV-2 vaccine was developed by David Knipe and Lynda Morrison.

      The 2011 papers you refer to about a HSV-2 ICP0- mutant virus are from my own laboratory…..the name of this virus is HSV-2-0dNLS. It is live-attenuated and is an excellent HSV-2 vaccine, but there is no company that has yet adopted my lab’s HSV-2 vaccine approach.

      Finally, the ACAM-529 vaccine is only entering a Phase I clinical trial now, and these should hopefully be completed by Summer 2014. How the ACAM-529 vaccine performs in clinical trials remains to be seen, but I am cautiously optimistic that it will be a major step forward.

      All I have seen over the last three years suggests to me that Sanofi Pasteur is legitimately trying to advance the HSV-2 ACAM-529 vaccine to clinical testing, but the process is just very slooooooooooooooooow.

      - Bill H.

  16. Mike August 20, 2013 at 6:50 pm #

    What are your thoughts on the Phase 1 trials that are starting in Australia by Coridon? Does it look like they are on the right track or just more hype?

    • Bill Halford August 20, 2013 at 7:37 pm #

      Hi Mike,

      I have heard many references to the Coridon trial, which I believe is affiliated with Dr. Ian Frazier’s group. However, I have yet to see a detailed explanation regarding (1) the active ingredients in the Coridon HSV-2 vaccine or (2) the supporting data that the approach works. If you are aware of some details, please let me know. To date, all I have seen is press releases that talk in vague terms about a promising new HSV-2 vaccine. If this is an accurate summary of the available info, then your guess is as good as mine regarding whether the Coridon HSV-2 vaccine is a substantive new idea or is just hype.

      - Bill H.

    • Tim August 21, 2013 at 1:05 am #

      I think they are very excited I called about the trials and the schedule they have set is very aggressive…. It looks like thy are trying to catch up to genocea … I think they will catch up and bypas genocea …. Especially since they are handling the more difficult and expensive trials up front which are the non infected individuals … Then they will investigate the theraputic properties which I expect to be good having read cordons articals leading up to this point…plus they have complete governmental support for the Success of this vaccine since Queensland is social medicine and costing them a heafty sum annually. If they succeed they will have cured cervical cancer and all diseases caused by hsv1… They will begin to be known for these achievements and even more investment capital will flow into this developing vaccine engine. I wish we were seeing more of this in the USA.
      My question is what’s about epsteins barr and hsv1 aren’t these the
      500 pound gorillas in the room :)
      Can your research be applied to these viruses or even aids.
      And thank you for being such a great and caring researcher ….. You will go far in life …. I’m sure
      Take care
      Tim

      • Bill Halford August 21, 2013 at 3:17 pm #

        Hi Tim,

        As I have addressed elsewhere in the comments previously, devising an effective HSV-1 vaccine is no more challenging than devising an effective HSV-2 vaccine. I don’t foresee any technical problems in devising and deploying a live- and appropriately-attenuated HSV-1 vaccine. The only real issue is (1) the source of funding for such work and (2) the path forward to human clinical trials for a live-attenuated HSV-1 vaccine. Scientifically, I see an effective HSV-1 vaccine as being a much easier goal to achieve than a HSV-2 vaccine, because (on average) clinical isolates of HSV-1 are far less aggressive than clinical isolates of HSV-2. A less aggressive virus (like HSV-1) generally translates into an easier target to control by immunization.

        Regarding EBV (Epstein-Barr Virus), this is a fundamentally different virus and is really a different topic of discussion. If scientists and clinicians are having a hard time persuading the pharmaceutical industry that there is an economic incentive to go after a HSV-2 genital herpes vaccine, I think that the economics (cost-benefit ratio for a company) of a EBV vaccine are a far steeper slope to climb. Speaking in general terms, companies do not invest tens of millions of dollars in vaccine development unless they believe that there is a major demand / large enough market to offset the multi-million dollar costs of a successful vaccine trial with a biomedical product that will be profitable in less than 10 years. I think that is a hard case to make for EBV, and unlike HSV we lack good animal models of EBV infection to work out all the technical details of what a good EBV vaccine should look like.

        - Bill H.

        • Tim July 24, 2014 at 11:15 pm #

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

  17. Warren September 2, 2013 at 6:55 am #

    Dr. Halford,

    Thank you very much for your dedication and leadership in HSV research!

    You state that many other viruses have been controlled or eradicated with live-attenuated vaccines that have been developed since the 1700’s. Why is the FDA concerned about development of these types of vaccines now, or is it only concerned about development of attenuated HSV-specific vaccines? Aside from the many misconceptions held about the virus in the 70’s that resulted in the subunit approach, are there any reasons to explain the current state of phobia surrounding live-attenuated HSV vaccines such as yours?

    Related to the hassles of vaccine development, how are pharmaceutical companies able to provide new, FDA-approved influenza vaccines year after year? Do they simply “tweak” approved, grandfathered vaccines for specific influenza strains showing that year?

    I’ve been infected with genital HSV for over 15 years now (unsure of type). Potentially, how might your vaccine provide therapeutic benefit to people like me who’ve had regular yet infrequent outbreaks over many years? Would our immune systems not already be very efficient at recognizing the virus?

    Keep up the great work!

    Regards, Warren

    • Bill Halford September 2, 2013 at 4:24 pm #

      Hi Warren,

      Three great questions, and I will address them in reverse order.

      Question 1. “How might your vaccine provide therapeutic benefit to people like me who’ve had regular yet infrequent outbreaks over many years? Would our immune systems not already be very efficient at recognizing the virus?”

      Please see my response to Tanya’s question, which I posted today. The majority of scientists believe what you claim that people with HSV-2 already have an efficient immune response to HSV-2 and this cannot be improved upon, thus meaning that a therapeutic vaccine would not be feasible. Long story short, I have seen too much independent data from too many independent sources over the year to buy this interpretation. There is considerable room for immune responses to be regulated (suppressed), and this may be part of what is happening in people who have frequent outbreaks of genital herpes (i.e., active regulation / suppression of your HSV-2-specific immune response). This begs the question…..why would the adaptive immune response suppress itself?

      The answer is simple……to prevent autoimmune diseases. Your bone marrow and the thymus do a nice job of filtering out self-reactive lymphocytes, and probably remove than 99.999% of self-reactive lymphocytes are removed by such “central tolerance” mechanisms. However, a few self-reactive lymphocytes leak out nonetheless, and thus we also have “peripheral tolerance” mechanisms (like T-regulatory cells) that help ensure that a single self-reactive lymphocyte does not turn into an autoimmune disease. There is very strong evidence that some persistent viruses can exploit T-regulatory cells to dampen the antiviral immune response against virus-infected cells. Same may be true of HSV-2. If you run with this hypothesis, a therapeutic HSV-2 vaccine could serve to reprogram or “reboot” the adaptive immune system so it does a better job after a therapeutic vaccination of combating recurrent HSV-2 infections.
      ————

      Question 2. “Related to the hassles of vaccine development, how are pharmaceutical companies able to provide new, FDA-approved influenza vaccines year after year? Do they simply “tweak” approved, grandfathered vaccines for specific influenza strains showing that year?”

      Great point. I have no idea how the live influenza vaccine sneaked past the gauntlet of regulatory concerns surrounding live viral vaccines. Perhaps part of it is that influenza virus kills a significant number of people every year (particularly amongst the elderly). Thus, it could be that the relative risk of a live influenza vaccine is much easier to justify knowing that a live influenza vaccine has the potential to literally save tens of thousands of lives every year. Interestingly, the live influenza vaccine (FluMist) is supposed to be a lot more effective than the influenza vaccines based on other approaches.
      ————

      Question 3. “Aside from the many misconceptions held about the virus in the 70’s that resulted in the subunit approach, are there any reasons to explain the current state of phobia surrounding live-attenuated HSV vaccines such as yours?”

      The fear of live vaccines is not HSV-specific. In large part, I believe the turn to subunit vaccines in the 1980s was driven by the recombinant DNA technology revolution. Suddenly, by the early 1980s, we had the technology to clone pieces of DNA at will, as well as the technology to rapidly sequence these pieces of DNA. By the 1990s, we were quite adept at this and could clone almost anything. So, without question, the turn away from live-attenuated vaccines to subunit vaccines was based on (1) the technology that made the new “subunit vaccine” approach possible coupled to (2) an overly simplistic / naive belief that subunit vaccines should be just as good as “more dangerous” live-attenuated vaccines. If you buy this argument, then why shouldn’t all of our vaccines be based on subunit vaccines?? All the protective benefits with none of the risks!!

      In the 1990s to early 2000s, we saw scores (hundreds?) of such viral subunit vaccines fail in human clinical trials. God only knows how many failed HIV vaccines there have been, and most of these were based on safe subunit vaccines that all sounded reasonable on paper. The fact of the matter is that subunit vaccines do not look anything at all to the immune system like a real viral infection; they are poor mimics and thus tend to do a poor job at training the immune system to recognize a real virus. The second error in logic is that “live-attenuated vaccines” can me made to be very safe. Yes, the oral polio vaccine has some problems……it was also derived in the late 1940s / early 1950s…….I think we have slightly better technology today for the genetic engineering of live-attenuated viruses. In other words, just because the oral polio vaccine is dangerous does not in any way, shape, or form mean my lab’s live-attenuated HSV-2 vaccine is going to suffer from the same problems.

      Fast forward to 2013, the problem today is that noone who sits on a regulatory FDA panel ever sees an investigational new drug application for a live-attenuated vaccine. So, it is not that live-attenuated vaccines necessarily became more dangerous, but rather all the scientists who have first-hand knowledge of (1) how to get a live-attenuated vaccine approved (e.g., Maurice Hilleman, Alfred Sabin) or (2) who have sat on the regulatory side of the table that deemed a live-attenuated vaccine preferable to unchecked viral disease have shuffled off this mortal coil. Yes, our forefathers had these conversations, and decided that live-attenuated viral vaccines were preferable to unchecked viral disease in the human population. Our generation has simply never had to have this conversation, and so were all hemming and hawing without any clue how to proceed……I am as guilty of this as anyone.

      I think it is time to get our friends at the FDA to revisit the pros and cons of live-attenuated vaccines, and restart the conversation.

      So, Warren, I agree that “misconceptions” are top at the list for why we are not considering a live-attenuated HSV-2 vaccine today. I think the fact that is important to remind regulators of is that the “live viral vaccine” approach has, hands down, led to the control / eradication of more viral diseases than any other approach in the history of medicine.

      I close by quoting the lyrics of a RUSH song entitled “Witch Hunt,” which sort of sum up where the FDA seems to be today in its willingness to consider new live-attenuated vaccines of any type:

      “Quick to judge
      Quick to anger
      Slow to understand
      Ignorance and prejudice
      And fear walk hand in hand…”

      - Bill H.

  18. Peter September 8, 2013 at 2:07 pm #

    Hi Bill
    Perhaps you could clarify a few points on the differences between EBV, HSV1 and Shingles etc.

    Reason for query…I have suffered from HSV1 since childhood and it is affecting pain in my eyes, ears and scalp. Four years ago I received the shingles vaccine and like magic my outbreaks ceased.
    They have just started again, this time with underarm swelling and am wondering whether my response to the shingles vaccine is anecdotal?
    Also, would a second dose of shingles vaccine have any harmful effects? Merck does not have research data to support top-up.

    • Bill Halford September 15, 2013 at 10:57 am #

      Hi Peter,

      Please forgive the delayed response. I have been up to my eyeballs with medical school teaching responsibilities.

      At the bottom of this post, I will cut-and-paste and a paragraph from a book chapter I wrote two years ago that clarifies the relationship between EBV, HSV-1, and shingles…..the bottom line you need to know for now is that these are 3 of the 8 known human herpesviruses.

      The next thing you need to know is that Epstein-Barr Virus, cytomegalovirus, and HHV-6, HHV-7, and HHV-8 live in blood cells (macrophage, B cells, or T cells), and thus really don’t have much to do with herpes simplex virus 1 and 2 beyond sharing a common evolutionary ancestry….dinosaurs would have had herpesviruses…..they have been around for eons…..today they are found in fish, crocodiles, seals, kangaroos, oysters. Collectively, there are more than 130 known herpesviruses, and 8 of them infect humans.

      So, now having addressed all of the irrelevant viruses above that bear the word “herpesvirus” in their name, we come to three human viruses that are close relatives: HSV-1, HSV-2, and VZV. HSV-1 and HSV-2 are, as you know, incredibly similar viruses. Varicella-zoster virus (VZV) is also a very similar virus, and shares at least 50 (if not 60) genes in common with HSV-1 and HSV-2. To put a ballpark number on it, VZV is 25 – 50% similar to HSV-1, whereas HSV-2 is ~98% similar to HSV-1.

      Elsewhere in this blog, I refer to a French study that reported something comparable to what you describe above: http://www.dovepress.com/efficacy-of-the-anti-vzv-anti-hsv3-vaccine-in-hsv1-and-hsv2-recurrent–peer-reviewed-article-OAJCT-MVP

      The short answer to your question is that, “No it would not hurt you to get another shingles vaccine.” The difference between the “chickenpox vaccine” and the “shingles vaccine” is that the shingles vaccine contains a 13-fold higher concentration of live-attenuated VZV Oka strain virus in each shot. So, if this approach is going to work, it would make sense that the shingles vaccine would be better than the chickenpox vacccine (because there is 13x more virus available to engage your immune system).

      Regarding why it might work is that VZV and HSV-2 share a lot of viral proteins in common. The reality is that this is how we stopped the spread of the human disease smallpox……we immunized people with a similar, but distinct virus, originally isolated from the cowpox lesions that cows get on their udders. This “cowpox virus” was not identical to the “smallpox virus,” but they had enough in common that the cowpox vaccination elicited an immune response that CROSS-PROTECTED against its close cousin the smallpox virus. The cowpox virus was first isolated by Edward Jenner in the 1790s, and he published a paper in 1798 reporting the cross-protection against the deadly smallpox virus (which killed 25% of Europe’s population on more than one occasion). After 1798, the virus was passed from vaccine recipient to vaccine recipient who developed a pock lesion at the site of vaccination that was loaded with the vaccine virus. Eventually, the virus came to be known as the “vaccinia virus,” and this is precisely the origination of the term “vaccination.” Originally, the term was introduced in contrast to the term “variolation.” Variolation meant to deliberately inoculate people with the virus that caused smallpox (i.e., the variola virus). Variolation did protect people against smallpox, but 1-2 % of people variolated developed smallpox disease and died. In contrast, “vaccination” was a much safer alternative and yet still elicited protection against smallpox. Louis Pasteur developed a “rabies vaccine” in the late 1800s, and so named the procedure in honor of Jenner’s discovery of the “vaccination” procedure to prevent smallpox. Hence, Louis Pasteur (nearly 100 years later) gave us the modern meaning of vaccination, which means “injecting someone with a benign substance that is antigenically related to a disease-causing microbe in order to elicit an immune response that is CROSS-PROTECTIVE against the disease-causing microbe.”

      I digress. The relevant point is that we cured smallpox with a SIMILAR, BUT DISTINCT vaccinia virus that was derived from cowpox. Likewise, many countries use the BCG vaccine to reduce the incidence of tuberculosis caused by Mycobacterium tuberculosis. The active ingredient in the BCG vaccine is a related bacterium known as Mycobacterium bovis…..SIMILAR, BUT DISTINCT from the agent of tuberculosis.

      So Peter, yes, there is a historical precedent for the phenomenon you describe of using VZV which is SIMILAR, BUT DISTINCT from HSV-1 in order to elicit an immune response that is CROSS-PROTECTIVE against diseases caused by HSV-1. If this is true, I note that a live-attenuated HSV-1 vaccine would be more effective as a therapeutic vaccine, as there would be 99.9% similarity to your HSV-1 virus as opposed to the 25-50% similarity of the VZV vaccine. However, the difference is that you can get a shingles vaccine today, whereas a live-attenuated HSV-1 vaccine is still far off on the horizon. I would not necessarily predict that VZV vaccination would be CROSS-PROTECTIVE against HSV-1 or HSV-2, but if it works, then who am I to knock success?

      Thanks for the interesting query.

      - Bill H.
      ———————————————-
      More formal response on relationship of HSV-1 to other human herpesviruses……

      1. Prologue
      Most virus families such as the picornaviruses are similar enough in genetic content to be meaningfully discussed as a group. This is not the case with the herpesviruses. The >130 known herpesviruses employ a conserved set of ~40 enzymes and structural proteins to synthesize virions that are indistinguishable from one another (Davison, 2002; McGeoch et al., 2006). All herpesviruses appear to establish life-long infections in animals that oscillate between relative states of latent versus productive infection. Beyond this, the similarities quickly disappear. For example, herpes simplex virus establishes life-long infections in neurons using a complement of ~75 genes, whereas cytomegalovirus relies on ~200 genes to establish life-long infections in monocytes (Murphy et al., 2003). This review will focus on herpes simplex virus such that the biology of a single herpesvirus may be considered in some depth. In particular, herpes simplex virus 1 (HSV-1) is one of the easiest human herpesviruses to study because it replicates to high titers, is amenable to genetic manipulation, and recapitulates most aspects of human infection in animal models. Thus, HSV-1 provides a powerful system to explore the many gaps in knowledge that exist at the interface between virology and immunology.

      In recent years, it has become apparent that host interferons play a more pivotal role in the biology of HSV infections than was previously recognized. The central tenet of the current review is that HSV exploits the host interferon system as a negative-feedback mechanism that controls the timing of the virus’s exit from the productive cycle of replication. The intensity of interferon-inducible repression of HSV replication varies over several orders of magnitude (Halford et al., 2005a). Thus, when host interferon signaling exceeds a critical threshold, it is possible that HSV’s interferon antagonists (ICP0 and ICP34.5) may fail to accumulate such that HSV is rendered sensitive to repression by the interferon response. Such an interferon-dependent shutoff mechanism might endow HSV with the capacity to cease all viral protein synthesis just as CD8+ T-cells are preparing to destroy HSV antigen+ cells. Unlike cytolysis by T-cells, interferon-inducible repression may be reversible. Once the local immune response wanes, a subset of HSV-infected neurons may re-enter the productive cycle of HSV replication weeks to months later.

      It is unlikely that the principles discussed herein are unique to HSV. Rather, the opposing forces provided by interferon-dependent repression and virus-encoded interferon antagonists may be exploited by many herpesviruses to regulate their oscillations between latent and reactivated infections. Likewise, most persistent viral infections may be described as a balance, or equilibrium, that is achieved between the host immune response and a virus that avoids clearance by this host response.

      Students are generally familiar with the concept that a process that is static to the eye may, in fact, be controlled by two equal and opposing forces. Therefore, we wish to suggest that students might grasp the biology of persistent viral infections more readily if these processes were described in terms of an equilibrium between virus and host. Aside from the simplicity of the approach, it accurately reflects the weight of evidence that the host immune system plays an integral role in restricting the spread of most, if not all, persistent viral infections. Below, we describe the in vivo biology of HSV infections in such terms.

      • Peter Rempel March 9, 2014 at 9:22 pm #

        Hi Bill
        You have been very helpful for my HVS-1 treatment options in the past.
        I have a further question. Since the last acyclovir treatment (200mg TID for 5 days) in the Fall, my nasal and facial lesions have not reoccurred until now.
        They have just started last week and typically they seem to increase in severity until they eventually stop. As most GPs have little expertice with viral treatment, can you please tell me whether it is advisable to begin acyclovir treatment upon onset of symptoms or is it better to let the body fight off the viral cascade by itself? Will acyclovir eventually lose it’s effectiveness if used numerous times? What dose regimen for facial and nasal outbreaks are indicated? (dose x days)
        Thanks in advance for all your efforts for myself as well as all of the other HVS 1&2 sufferers.

        • Bill Halford March 9, 2014 at 9:35 pm #

          Hi Peter,

          I would suggest that you start acyclovir treatment at the first inkling that you may be having an outbreak.

          No, the acyclovir will most likely not lose its efficacy over time. It is possible that the particular HSV-1 isolate that inhabits your body could become resistant to acyclovir, but it is simply not very likely. I won’t bore you with the underlying reasons, but the bottom line is that (1) drug-resistance is a huge issue with HIV infections, but (2) drug-resistance is far less common with HSV-1 and HSV-2. So, just use acyclovir as needed, and don’t worry about the treatment losing its effectiveness unless you observe this to be an actual issue (i.e., not just a theoretical concern).

          Regardless of where herpes outbreaks occur (nose, face, mouth, back, genitals), I would recommend antiviral drugs such as acyclovir from the time you first feel symptoms and continuing for until 3 days after you feel the threat of an outbreak has passed (i.e., typically 7 to 14 days).

          If you are concerned about the effectiveness of acyclovir, valtrex will most likely give you a greater therapeutic effect because it is better absorbed out of your intestine (i.e., valtrex is more soluble than acyclovir).

          - Bill H.

  19. Peter September 18, 2013 at 12:29 pm #

    Hi again Bill,
    Your information has been both enlightening as well as very helpful in my search for HSV1 outbreak relief. Also, it’s a relief to know my improvement was not placebo derived.
    Until retirement earlier this year, I have been involved in the Canadian pharma/biopharma industry in multiple therapeutic areas including ID. I relate this to emphasize the wonderful service you provide with this blog. No one else over the years has provided such a complete picture of the relationship between the viruses, nor offered the clear option for re-vaccination. I have already received another VZV vaccine dose yesterday and if you wish, I am willing to share outcomes in the future. Thank you very much Bill.

    • Bill Halford September 18, 2013 at 2:56 pm #

      Hi Peter,

      I would absolutely be fascinated to hear whether or not you feel like the 2nd round of the VZV / shingles vaccine helps you out. Thanks for the feedback.

      - Bill H.

      • Peter November 24, 2013 at 3:28 am #

        Hi Bill
        Within a week of receiving the shingles vaccine, I got a severe HSV1 outbreak. It required 5 day oral antiviral meds to suppress. Since then all is well. I’m hoping that the outbreak was coincidental, or that the immune response took a while to develop. Any thoughts would be welcome.
        Thanks
        Peter

        • Bill Halford November 24, 2013 at 2:30 pm #

          Hi Peter,

          Vaccination routinely elicits an inflammatory response and a fever. HSV-1 cold sores are conventionally known as fever blisters for a good reason….when you have a fever, this serves as a trigger for an outbreak.

          I would assume that any vaccination, particularly one that induces fever and aches, would increase your odds of an outbreak. Hopefully, your outbreaks will lessen in the future.

          - Bill H.

        • Tim November 26, 2013 at 10:26 pm #

          Bill I have a question… I have been having this ongoing battle with uvitus that I believe is hsv related…. I have tried everything …. The only thing that did work was a hsv clinical trial but it only helped for 3 months …. Every day and every night I research a possible solution. I was reading that Rutgers discovered that a foot fungus cream Ciclopirox made HIV infected cells die …. I also researched that the FDA fast tracked another drug with the same active ingredient and did not require animal trials… Next I found a researcher in England that is attempting to remove the immune dampening part of these drugs so they can be used as anti viral’s …. I was thinking it might work for hsv as well
          My eyes are getting worse there are floaters everywhere so I thought why not try rubbing the foot cream on my stomach to see if it reduces the inflamiation in my eyes…. It did…. But I don’t know why it is working …. Can you please conduct an experiment on this and tell me what’s really going on…. All I know now is that it is working … Please tell my why… I’m hoping its killing the hsv?

          Thank you
          Bill
          Ps.
          I think you are doing a very good thing talking to people as you do

  20. Rivers October 5, 2013 at 2:25 pm #

    Dear Bill H

    Its my understand if an aggressive treatment of Famvir and Acylovir for 90 days is applied during the 14 days initial or an acute out break of HSV2 this could have dramatic effects in
    preventing the reoccurrence or the presents of IGG antibodies from developing is this true? Or can it be empirically stated the once there is a HSV 2 outbreak the IGG will eventually be produced at some point?

    • Spencer October 17, 2013 at 3:30 pm #

      Hello,

      This is interesting news for me. I was visually diagnosed 4 days ago with genital herpes with symptoms having started 8 days ago. I am on day 3 of Valtrex where I am taking 2 pills twice a day. Are you suggesting I request a longer initial dosage period? 90 days or 3 weeks? I am willing to try anything! Thanks

      • Bill Halford October 18, 2013 at 7:52 am #

        Hi Spencer,

        There have been numerous studies dating back to the 1980s where genital herpes patients go on prophylactic acyclovir or valtrex for multiple years. While I think there are potential downsides of life-long valtrex, I certainly think there is good reason to believe that valtrex throughout the primary infection (at least for the first month) is a good idea to minimize viral seeding of the nervous system. Support groups are loaded with people who have lived through this, and they are a better source of information than myself or my blog.

        - Bill H.

  21. Esme November 1, 2013 at 4:21 pm #

    Should your study move onto testing HSV2 positive patients, would I be eligible to apply? I’m from the UK but the suffering and mental/physical pain this is putting me through, I would temporarily re-locate for as long as needed.

    • Bill Halford November 1, 2013 at 4:59 pm #

      Hi Esme,

      I would hope to set up a clinical trial that would be open to anyone who could travel to the clinical trial site, regardless of your country of origin. I still need to find a site, and hammer out such details, but my personal preference would be to set up a clinical trial for HSV-2 seropositive patients in exactly your situation. That is, I believe that the appropriate place to begin clinical trial testing is with patients who are (1) HSV-2 seropositive and who (2) currently suffer from the mental/physical pain of frequent to chronic genital herpes recurrences that are not currently alleviated by any available treatments.

      The advantage of this type of clinical trial is that (1) there is no rational argument that could be offered that a live-attenuated HSV-2 vaccine could be any worse than what you are currently experiencing, (2) such a clinical trial would rapidly yield safety data in human subjects which would allow me to directly address the million-dollar question of “Is a live HSV-2 vaccine safe enough?”; and (3) we might be surprised to find that a live-attenuated HSV-2 vaccine offers a viable therapeutic approach to reduce the symptoms of HSV-2 genital herpes in a significant fraction of patients who are in your situation and currently living with chronic herpes.

      Thanks for your inquiry.

      - Bill H.

      P.S. I don’t think relocation would be required. While you might need to travel to a clinical trial site on 2 or 3 occasions, most vaccination booster series are given with 3- to 6-week breaks in between shots. Like all vaccinations, the shot itself would take only a few minutes. Probably cheaper to travel to a clinical trial site 2 or 3 times (for a 1- to 2-day visit), as opposed to relocating somewhere new for 1 to 3 months.

  22. Esme November 2, 2013 at 8:32 am #

    Bill

    Thank you for your quick response!

    I certainly tick the boxes required.

    Thank you for your info, I look forward to any progression made.

    P.S Herpes Virus Association is the charity run support for Herpes in London, if you were to contact them, I’m sure if they made it public in England what you were trying to do, you might be able to get some funding help from them? If you Google HVA into the computer and their details will come up.

    Keep up the good work, thank you!

  23. Mat November 12, 2013 at 7:56 pm #

    Hi Dr Halford,

    I find it interesting that the makers of the chicken pox vaccine do not want to expand their pipeline to cover hsv2/1

    Mat

  24. paul November 23, 2013 at 9:15 am #

    I’m an immune suppressed transplant patient with hsv2 . With very frequent outbreaks. Almost continuously. Have I any hope of getting any relief or will I just have to live with this. Will these new vaccines help the likes of me

    • Bill Halford November 23, 2013 at 10:58 am #

      Paul,

      I am sorry to hear of your circumstance. Yes, you are correct that the immune system constantly does battle with so-called “latent” HSV-2 infections, and actively holds them down. When people are chronically immunosuppressed for clinical reasons (organ transplant or autoimmune disease), the scenario you describe is all too common and valtrex probably only takes the edge off, but does not really hold HSV-2 down without some more help from the immune system.

      It is indeed possible that a real therapeutic HSV-2 vaccine could help you out and help re-educate / re-focus your adaptive immune response on the enemy that is HSV-2. Wish I could tell you that more clinical trials of what I think would be an effective therapeutic HSV-2 vaccine are imminent; they are not, and Agenus HerpV and Genocea GEN-003 are a joke based on the data I have seen presented thus far. If a scientist uses the word “percentage” to describe a reduction, that is typically a bad sign. We should be looking for “fold reduction” not “percentage reduction.”

      I suspect that your immunosuppressed status would knock you out of contention for the ACAM-529 vaccine trial, but it cannot hurt for you to explore this option. Given your unusual circumstances, I would encourage you to e-mail me directly. Not sure that I can help, but you may have other questions that are better discussed in a non-public forum.

      - Bill H.

      • paul November 23, 2013 at 2:20 pm #

        Bill could you tell me what effect tacrolimus and azathiaprin would have on anti body production. Would Igm and igg production be stopped or just slowed down in a primary hsv2 infection and how would that affect the course of outbreaks.

  25. paul November 23, 2013 at 3:12 pm #

    I noticed you recommend longer duration of valtrex to reduce viral seeding in CNS. If such seeding takes place is it possible to reduce it or is it staying there ?

  26. Olav Lunde December 1, 2013 at 5:38 pm #

    Hey Bill, l love your blogg, this is a place we all can get a lot good information, l just got HSV-2 4 months a go out of the blue and like the others in here l`m desperate for a cure/vaccine,
    l have been together with my wife for 4 years and l now l suddenly have it, but she don`t have it.

    I`m from Norway Oslo and my Dr here did not speak to me about it at all, he just printed out the medicine prescription and told me good luck Mr, lol.

    l have been reading every day for past 3-4 months on it and l found your blogg today, it made me very happy. I have contacted Dr. Anna Wald she is famous for her research on HSV-2, she also talked about Genocea GEN-003, but l don`t know what good they are doing for the HSC-2, l asked here how long until she thought it would be a vaccine for commercial marked, she told me 5-7 years, that is way way to long l think, but l got to take here word for it.

    l would go any where any time to try any vaccine right now. l have a outbreak one`s every month now, 24 days between them, and it last about 10 days every time:( sow my sex life is more or less over for now. My english is not sow good, but l can´t say l could see any where that you worte about a time frame for a vaccine, and is there any place people like me with HSV-2 can be testing pet`s for a future vaccine ? ? I think most of us are willing to try any thing.

    One thing l will try is to take 250 mg of Valtrex twice a day one in the morning and one before sleep for one year to see if l can isolate it down to just 1-3 outbreaks a year, l see some of the Norwegian Dr saying that it`s been proven here in Norway that it can decrease the outbreaks and it will decrease the chances to transmit the HSV virus to you partner, but of course it`s still
    contagious but less becouse of the few outbreaks. But this i just what they wrote about a study here in Norway. My biggst problem is that Valtrex is sow expensive, it`s 40 pound per box that is a lot of money for one year.

    Hope to hear from you Bill:)

    Best regards
    Olav
    Norway.

    • Bill Halford December 5, 2013 at 6:56 pm #

      Hi Olav,

      Glad to hear you have found information on the blog helpful. By the way, your English is a lot better than my Norwegian!

      Sorry to hear about the constant outbreaks; yes, I agree that this is horrible and if regulatory agencies in the U.S. and Europe ever pull their heads out of their bums, then they will realize that the idea of “saving the world from the dangers of a live HSV-2 vaccine” is about as stupid as they come, as the symptoms that you (and millions of others) are living with day-in and day-out is a hell of a lot worse than anything that my lab’s live-attenuated HSV-2 vaccine (or any other of which I am aware) could possibly do to you relative to the symptoms of constant HSV-2 genital herpes outbreaks.

      If I can manage to get a therapeutic HSV-2 vaccine started somewhere in this wide world of ours, I will certainly advertise that information here on this blog, in precisely the same way that I have posted information on my thoughts on the promising HSV-2 ACAM-529 trials that are starting in Bethesda next month.

      In the meantime, I would suggest that you should give valtrex a go, and if money is an issue then you may wish to consider a generic form of acyclovir. In general, acyclovir is less effective than valtrex (less bioavailable), but does the trick for many people. Your case sounds challenging, so valtrex is your best bet. However, you can certainly give the less expensive acyclovir a go (i.e., acyclovir is about 10% the cost of valtrex), and maybe it will help you out as well.

      Good luck with this…..hope you can get this under control.

      - Bill H.

      • Olav Lunde December 5, 2013 at 7:59 pm #

        Thank you sow sow sow much Bill for writing back to me, l`m sow happy right now, you are the light in the tunnel for most of us in here, l know it`s gone take many years before we got HSV-2 vaccine, but l`m going to do what ever it takes to get this under control, l can`t let this take over my life any more, sow l will try to find the right dose to take every day and see if l more or less put it in checkmate for as long as possible, l know it will always come back 2 or 3 time a year and that`s okey.

        After 2-3 hundres of hours of reading on HSV-2 l can see that there are many different opinions from different Dr, seems that many doctors who write about HSV-2 do not really know 100% how the virus behaves and how it really transmitting, and they all say that it is transmitted through wounds / lems, but it says little about it is because the blisters rupture or that it will come fluid out of the urethra containing HSV -2 or that it is HSV-2 fluid comes out from the skin around where the old outbreaks have been. I really don`t understand how it`s transmitting when you not sick, l can se that it`s difficult to see when your going to have a outbreake, but lf l follow up on my areas l will feel and see the small
        blisters developing, sow when l know l don`t have the blisters it should be less chance of transmitting the HSV, but that just my opinion.

        The Norwegian health sytem writes just the same about HSV-2 no matter which article l read, completely useless information that I have read, funny because your info about HSV-2 is 1000% more valuable than my own health state info, there is no exact info there:(

        As I said in the last email, here in Norway l feelt that the Dr stigmatize me after l got the diagnosed with HSV-2, but that just life. As I also mentioned to you, if under any circumstance or chance`s would be possible in the future to pay my way into a HSV-2 vaccine test sow please be kind and let me know Bill. I`m willing to pay dearly to get this virus stopped. But l know you all work under really strict US rules, and roles are roles, but l can be the european lab rat:)hehe.

        Again thank you sow much Bill l will follow you for many ears sow you will hear from me again:)

        Best regards
        Olav:)

  27. Warren December 6, 2013 at 5:37 am #

    Dr Halford,

    Thank you again for your dedication and leadership in HSV research!

    I’m hoping that you may be able to comment on the following questions regarding HSV that I cannot seem to find the answers to:

    - I understand that antibodies are typically passed to a child by its mother, both while in the womb and after birth while breast feeding. I presume this would apply to HSV-2 antibodies provided the mother had sufficient time from exposure to develop a full immune response. Would that child also benefit from any long-term protection against the virus or would any benefit cease at the end of breast feeding? If there is a long-term benefit to the child, could this come from the father alone (i.e. long-standing history of hsv-2 by father prior to conception, with no history of hsv-2 by mother)?

    - I read an article in Scientific American (Sep 10, 2008) that stated children could inherit HHV-6 (Human Herpes Virus 6) from their parents DNA. It also stated that viral integration could disrupt chromosome function and spark a plethora of complications, including cancers. If that view is still held, is it possible for this type of thing to happen with the herpes simplex virus as well?

    - How likely would autoinoculation be for a long time sufferer of genital herpes? I ask because years ago when I first had outbreaks they would be on my penis, but more recently I’ve had them on my anus, buttocks and lower back/hip area. Would these outbreaks be distinct and separate from the primary area of infection years ago?

    - How long does the herpes virus survive outside of the human body? Are there any circumstances where the virus can survive away from its host for very long? What things would aid the virus in remaining viable outside of the body, and what things would destroy it (e.g. water, soap, light, heat, cold, chemicals)?

    Thank you for you interest.

    Sincerely,

    Warren

  28. tanya February 14, 2014 at 2:35 pm #

    Hi Dr. Halford,

    Is it possible to unknowlingly pass HSV-2 to your child ( 6 years old)? I’ve had it since before she was born, rarely get outbreaks, and they’re usually very mild, so I haven’t thought much of it. Should i be concerned about passing it to my daughter through touch, towels, baths, etc? My sister has HSV-1. Is that also a concern for transmission to my child genitally? Can HSV-1 cause genital lesions in children? I saw something on my daughter’s privates that looks like a lesion and am very concerned if it is. Thanks for any advice you may offer.

    • Bill Halford February 14, 2014 at 2:44 pm #

      Hi Tanya,
      The risk of transmission would be minimal. If you had herpetic whitlow (HSV on your hands / fingernail area), then that would represent somewhat of a risk. But by-and-large, genital herpes is transmitted by DIRECT CONTACT with the infected area…….not from the genital area via an intermediate (hands or toilet seat) to someone else’s genitals. The scenario that concerns you seems highly unlikely to me.

      - Bill H.

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