RVx: Better Vaccines for a Brighter Future

beautiful-lonely-girl-on-the-streetLonely image

 

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In this post, I address three questions about RVx’s new line of highly effective HSV-2 vaccines:

  1.   Why do we need an effective HSV-2 vaccine ASAP?
  2.   What makes RVx’s HSV-2 vaccines more effective?
  3.   How would an effective HSV-2 vaccine change the future?

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1. Why do we need AN EFFECTIVE HSV-2 vaccine ASAP?

The photos above tell much of the story.  The physical symptoms of HSV-2 infection are often not debilitating, but they are very often isolating.  In my conversations with HSV-2 sufferers, three recurring concerns are (1) fear of intimacy due to fear of hurting others as they were hurt when they contracted HSV-2; (2) isolation and depression; and (3) resignation that they will walk through life alone.  This is 90% of the story about why HSV-2 genital herpes is a damaging disease.

The other 10% of the story with recurrent genital herpes is that this can be far more than a “skin condition.”  I have spoken with many herpes sufferers who describe chronic nerve pain (as occurs post-shingles) and who experience 10 to 30 outbreaks of neuralgia or painful and swollen genital lesions per year.  For some patients, acyclovir or valtrex do not relieve these chronic disease symptoms that affect them 3 to 6 months out of the year.  Thus, for many, recurrent genital herpes is a chronic disease for which there is no effective treatment and from which they can find no relief.

Against this background, there are two immediate needs for an effective HSV-2 vaccine:

  1.  A therapeutic HSV-2 vaccine that may provide a new treatment option to those who currently live with chronic, unrelieved disease; and
  2.  A prophylactic HSV-2 vaccine that may be used to protect vulnerable partners in discordant relationships.

These are two real-world and immediate problems that cause suffering amongst millions.  There is no valid reason for delaying the delivery of potentially life-altering medicine in the forms of (1) the most potent therapeutic HSV-2 vaccine treatment possible for people who suffer with a chronic disease and (2) the most potent prophylactic protection to protect individuals in discordant relationships from the risk of contracting an HSV-2 infection.

For these reasons, Rational Vaccines (RVx) is exploring the possibility of offering clinical trials of a therapeutic live HSV-2 vaccine, Theravax‾², which is based on a well-studied live HSV-2 vaccine strain, HSV-2 0ΔNLS.  Once the safety of the Theravax‾² vaccine is established in Phase I Clinical Trials, RVx will be exploring the possibility of offering clinical trials of a prophylactic live HSV-2 vaccine, Profavax‾², as soon as possible.

Scientists will likely continue to debate the pros and cons of a live HSV-2 vaccine for years to come.  For my part, I am done debating.  RVx was formed to bring an effective live HSV-2 vaccine out of the shadows so that it can begin to (1) protect the vulnerable from new HSV-2 infections and (2) potentially help reduce the suffering of millions of people whose chronic HSV-2-induced disease is not alleviated by current antiviral drugs.  The relative risk of testing a safe and thoroughly vetted live-attenuated HSV-2 0ΔNLS virus in Phase I Clinical Trials pales in comparison to the assurance that millions of people will continue to needlessly endure lives filled with pain and hopelessness for as long as we lack a real HSV-2 vaccine that actually works.

The time for idle talk is past.  We have the opportunity to end the needless suffering caused by HSV-2 infections with a new class of live-attenuated HSV-2 vaccines that appears to be 50 times more potent than anything that has been tested in human clinical trials over the past 30 years.   Therefore, RVx was formed to put this question to rest and determine if a live-attenuated HSV-2 vaccine will be sufficient to (1) serve as a therapeutic HSV-2 vaccine and (2) serve as a prophylactic HSV-2 vaccine that protects vulnerable individuals (e.g., in HSV-discordant relationships) from the risk of acquiring HSV-2 genital herpes disease.

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2. WHat makes rvx’s HSV-2 VACCINES more effective?

RVx was created for the purpose of advancing the worlds’ first HSV-2 vaccine that is rationally-engineered to be 50 times more potent than synthetic HSV-2 vaccines (e.g., Herpevac, GEN-003, Agenus HerpV, Admedus) in its capacity to reduce and/or prevent herpes disease symptoms.

Numerous publications establish that HSV-2 0ΔNLS and other HSV ICP0‾ mutant viruses are exceedingly safe (avirulent) because they are hypersensitive to repression by the host antiviral response.  However, unlike HSV-2 glycoprotein subunit vaccines that have been failing in human clinical trials for 30 years, the live HSV-2 0ΔNLS vaccine introduces vaccine recipients to 9 to 19 different HSV-2 proteins.  This more “polyvalent” immune response elicits a protective immune response that is about 50 times mores potent than a HSV-2 subunit vaccine.

Regarding the published data on live-attenuated HSV-2 ICP0‾ mutant vaccines (like Theravax‾² and Profavax‾²), numerous pre-clinical studies demonstrate that HSV-2 0ΔNLS is vastly superior to the HSV-2 subunit vaccines that have been the mainstay of failed HSV-2 vaccine efforts for the past 30 years.  Specific citations include the following:

  1.  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012251
  2.  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017748
  3.  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0065523
  4.  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116091
  5.  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145228

Furthermore, the literature on the safety and superiority of live HSV-2 ICP0‾ mutant vaccines may be found in these reviews:

  1.  http://www.futuremedicine.com/doi/abs/10.2217/17460794.2.1.1
  2.  http://www.ncbi.nlm.nih.gov/pubmed/24837838

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3. WHAT MAKES RVX’S HSV-2 VACCINES MORE EFFECTIVE?

RVx will needs to complete its clinical trials to validate the safety and efficacy of the HSV-2 0ΔNLS vaccine in humans.  However, in the history of the world, there has never been a single example of a live (replication-competent) and appropriately-attenuated viral vaccine that did not succeed in controlling the intended viral disease.  Specific examples of diseases that were successfully controlled with live-attenuated viral vaccines include smallpox, yellow fever, polio, mumps, measles, rubella, and chickenpox.  Given the 100% track record of the approach, the odds are on RVx’s side that the live-attenuated Theravax‾² and Profavax‾² vaccines will be able to stop the epidemic spread of HSV-2 genital herpes.

Although numerous HSV-2 vaccines have failed in clinical trials over the past 30 years, these were all based on “subunit vaccine” concepts in which it was hoped that exposing vaccine recipients to 1 – 2% of HSV-2’s foreign proteins would be sufficient to elicit an immune response that was 100% protective against HSV-2.  In contrast, the live-attenuated Theravax‾² and Profavax‾² vaccines have the capacity to express 99.3% of HSV-2’s foreign proteins and this 100-fold increase in “antigenic breadth” underlies why RVx’s new line of live-attenuated HSV-2 vaccines are 50-fold more potent than any of the synthetic HSV-2 vaccines discussed to date.

Starting in 1974, the live-attenuated VZV Oka vaccine began to effectively control chickenpox in Japan, and thus was brought to the USA in 1995 where, immediately upon deployment, it started to curb the incidence and spread of chickenpox.  Today, many Americans age 20 and below have never seen a case of chickenpox because the live-attenuated VZV Oka vaccine was that effective.  The same dramatic reductions in HSV-2 transmission and disease are infinitely possible if we, for the first time ever, use a live-attenuated HSV-2 vaccine to stop the ongoing spread of HSV-2 to the 10 – 20 million people who are newly infected each year.

I note that VZV and HSV-2 are close relatives as they are both (1) herpesviruses that latently infect neurons and (2) they share about 60 homologous genes in common.  Given the live VZV Oka vaccine’s extraordinary success in stopping the epidemic spread of chickenpox, there is no reason to assume that a live and appropriately-attenuated HSV-2 vaccine will not be similarly effective in immediately starting to curb the epidemic spread of HSV-2 such that HSV-2 genital herpes may soon be joining smallpox and chickenpox in the history books as “diseases of the past.”

Rational Vaccines (RVx) was created for the purpose of executing upon this vision.  If herpes sufferers wish to show their support, then please email the addresses listed below and let RVx know which vaccine is of interest to you and why.

Future Theravax‾² Trials.  If you are interested in being considered for future clinical trials of RVx’s therapeutic HSV-2 vaccine, then please email rvx.therapeutic.vaccine@gmail.com and include your full name, phone number, permanent email address, and a brief description of your HSV-2-associated clinical condition for which you are seeking a better therapy.

Future Profavax‾² Trials.  If you are interested in being considered for future clinical trials of RVx’s prophylactic HSV-2 vaccine to minimize your risk of acquiring HSV-2, then please email rvx.prophylactic.vaccine@gmail.com and include your full name, phone number, permanent email address, and a brief statement of whether or not you are in a HSV-discordant relationship.

RVx thanks you all for your help and support, and we hope to repay the favor with an effective line of HSV-2 vaccines delivered ASAP.

– Bill H.

13 thoughts on “RVx: Better Vaccines for a Brighter Future

  1. devastated says:

    I am newly diagnosed and new to blog. It certainly has left me devastated, depressed and hopeless. Finding this site gives me a tinge of hope! Can you please tell me more on what your vaccine will be intended to do? Will it eradicate the virus from an infected individual or surpress it (such as Valtrex, but in vaccine form)?
    When might the trials for your vaccine begin? I know you can give specific but are we talking months, years?
    Thank you for your dedication and not forgetting about us sufferers.

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    • Herpes Vaccine Research says:

      Dear Devastated and Sam,

      You are asking parallel questions, so I offer a single response rather than write something similar twice.

      Devastated, regarding a superior line of HSV vaccines that are 50x better than GEN-003 and the improved diagnostic test that is similarly far better than current gG-based antibody tests (HerpeSelect, Theranos, etc), these products will be offered by Rational Vaccines Inc. (http://rationalvaccines.com/). The content for the website is done, but the process of working through web developer is taking far longer than I had hoped. Hopefully this will be remedied ASAP, as I (and many on this blog) are growing frustrated with a website that I thought would be launched by now. Once the content is up, the Rational Vaccines website will contain all of the info that addresses your questions. So, please check it out when it goes live…..I will announce on the blog when this is the case. It will not be a traditional biotech website, but will have all of the info (several layers worth of info) so that everyone can get to the bottom of what the vaccines do, why they work better than past herpes vaccines, and the same is true for the diagnostic test which is a separate but equally important issue.

      Sam, I would anticipate that a safety trial of the Theravax^HSV-2 vaccine (our lead vaccine, but we also have a Theravax^HSV-1 too) would take about 3 months to initiate regarding the vaccinations themselves, and there would be another 9 months of follow-up. Unlike all of the scam artists who operate in the vaccine space, I do not believe in blowing on horns and trumpets just because a Phase I Clinical Trial is planned. Once a Phase I Clinical Trial is complete, Rational Vaccines will have (1) a press release around the successful results of said trial showing that Theravax is safe, immunogenic, and reduces most herpes sufferers symptoms and (2) we will post a representative swath of data from the trial on the RVx website such that is immediately available to the world. Perhaps as early as December 2016.

      No promises on timeline though. I work on this about 80 or 90 hours per week, so rest assured that I am doing everything within my power to bring all of this into the light of day and make it part of the new reality that we will first be controlling symptoms and then stopping the spread of herpes in the human population. However, real science (not the hype and BS of Genocea, Vical, Admedus, and Agenus) that breaks fundamentally new ground takes time to do right. We have been getting herpes vaccines totally wrong (i.e., the scientific community) for 30+ years because we were “in a hurry” (e.g., failed Herpevac and GEN-003 are essentially the same vaccine with the exception of the addition of 300-likely-irrelevant amino acids from ICP4). I, on the other hand, am in no such hurry because it is a false notion that real science can be rushed. Rushing leads to mistakes, bad assumptions, bad hypotheses and conjecture become misinformation with the passage time as people repeat the same mistruths for decades, until the whole field descends into disarray and confusion about which direction is the correct path out of the quagmire created by humans who were “in a hurry” (creating confusion around bad herpes vaccine concepts for 30+ years).

      Someone told me once (not sure if this is true but it makes a nice story), that Napoleon walked into a barber shop and says to the barber about cut his hair, “I am in a hurry. So, please take your time.” In other words, I don’t have time for mistakes, so please do the job right the first time. That’s the reality of science. Good science takes three times longer than B.S., but the difference is that because you actually prove the underlying truth that is correct, noone has to come after you, sweep up the mess, and start from scratch again.

      Knowledge in the hereps vaccine space really is, for the first time in decades, moving forward and I believe that will be apparent when Rational Vaccines’ website goes live.

      I am working as hard as I can on this, but I cannot promise a timeline because it is not solely in my control but is a team effort involving dozens of people. So, when will a HSV-2 vaccine that actually works as a therapeutic vaccine and a preventative vaccine be available to the public? As soon as possible.

      Sincerely yours,
      Bill Halford

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  2. Sam says:

    Hi Dr. Halford,
    Thank you for taking the time out of your busy schedule to answer questions and provide updates.

    my question: I’ve read that phase 1 trials are usually not more than 1 year. Assuming that a phase 1 trial will be mainly confirming the safety of the product. How long would a potential phase 1 trial of theravax last?

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  3. Jon says:

    Hi Bill, just a couple of quick questions:
    1) Is there any evidence that your HSV-2 vaccine could be useful for preventing or treating oral HSV-1 infections?
    2) If RVx exceeds its funding goals, would it be feasible for the company to work on HSV-1 and HSV-2 vaccines at the same time?
    -Jon

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    • Herpes Vaccine Research says:

      Hi Jonathan,

      Rome was not built in a day. To date, a meaningful examination of the safety and efficacy of a live-attenuated HSV-2 vaccine in a Phase I Clinical Trial has not occurred once in the history of mankind. I would suggest that we should well and truly achieve this first milestone before we allow our focus and attention to drift to downstream questions such as you raise. For me, this falls into the category of “Don’t count your chickens until they hatch.” Once a live-attenuated HSV-2 vaccine “hatches” and is on the world stage, then I will entertain downstream questions such as you pose, but not until the first milestone is achieved.

      – Bill H.

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      • Jon says:

        Hi Bill,
        I really appreciate your fast response. I understand that you’re mainly focused on HSV-2, and how that could turn questions like mine into “downstream” questions which should be addressed later on. I also understand the rationale for primarily focusing on HSV-2: the physical effects are said to be more painful, and because it carries a greater social stigma than a cold sore, it’s more likely to be psychologically traumatic.

        However, I’m sure you’re fully aware that oral HSV-1 isn’t necessarily a walk in the park. Like most of the world’s population, I’m a carrier, but unlike most people, I’m aware of my status, mainly because I have an immune system that doesn’t seem to handle the virus very well. I experience prodrome symptoms (mostly lip tingling) on a very frequent basis, which significantly interferes with the my ability to be physically intimate.

        I guess I’m writing all this to let you know that there are people like me who anxiously await an effective HSV-1 vaccine and/or cure, and even if we’re not your primary focus at the moment, I hope you keep us in mind.

        Thanks for all the great work you do.
        -Jonathan

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  4. almeron says:

    je vous remercie grandement pour ce travail que vous faites. J’ ai eu a faire des examens . pour mes examens les résultats en IGM était négatif, mais ils étaient positif en IGG. Pour mon premier examen en HSV 2 le résultait était de 55.8 Ul/ml et en HSV 1 le résultat était 29 Ul/ml. Conclusion : Sérologie herpes simplex positive. Pour mon dernier examen en IGM c’était toujours négatif et iGG c’était positif uniquement pour le HSV 2 avec un résultat de 21 uarb/ml. En conclusion c’était écrit: Probable infection ancienne à herpes simplex de sero type 2. je suis en Afrique plus précisément au Cameroun. Si tout se passe bien je serai aux USA dans quelques mois. je suis volontaire pour les essaies cliniques. la mort ce n’est pas seulement quand on meurt, mais cette maladie aussi tue l’homme et vraiment je vous encourage fortement dans vos recherches tout en espérant grandement que la fin sera meilleure. je reste très optimiste. SVP Dr Bill s’il vous plait, expliquer moi un peu la signification réelle de mes résultats. je n’ai jamais eu de poussé, peut t être parce que ici en Afrique je consomme toujours assez de trucs ( plantes naturelles etc). mais je ressens toujours depuis 6 ans une sensation de chaleur au niveau des cuisses, jambes, pieds etc. c’est vrai que j’ai aussi eu un clhamydia qui tardé a guérir

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    • Herpes Vaccine Research says:

      c/o Google Translate

      I thank you greatly for the work you do. I have had to do exams. for exams results in IGM was negative, but they were positive by IGG. For my first HSV 2 review the result was 55.8 IU / ml and HSV 1 the result was 29 IU / ml. Conclusion: Serology herpes simplex positive. In my last review in IGM was always negative and IgG was only positive for HSV 2 with a score of 21 UARB / ml. In conclusion it was written: Probable old herpes simplex type 2 sero I am in Africa specifically in Cameroon. If all goes well I will be in the US in a few months. I volunteer for clinical try. death not only when we die, but this disease also kills the man and I really encourage you in your research while greatly hope that the end will be better. I remain very optimistic. Dr. Bill please please explain me about the real meaning of my results. I have never been pushed, can t be here because in Africa I always consume enough stuff (natural plants etc). but I still feel for 6 years a warm sensation in the thighs, legs, feet etc. it’s true that I also had a clhamydia which has delayed healing

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      • Herpes Vaccine Research says:

        Hi Almeron,

        It sounds like from your test that you have been infected with HSV-2 for some time (IgG-positive for HSV-2; IgM-negative for HSV-2). I am less certain about HSV-1 as one IgG test came back positive and the other came back negative.

        – Bill H.

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  5. swim2lakes says:

    Bill: Thanks for the work you do. MY life has been laid waste for 2 years by severe bodywide Small fiber and autonomic neuropathy. I am in suicidal levels of pain. I am homebound and hopeless. There are two culprits. My doctors think either that I am crazy or will not address these ideas, instead saying “idiopathic” I have HSV- 2 at least since 2009 that I never treated ( no debilitating outbreaks).. THIS year I learned the the intermittent huge outbreaks on the bridge of my nose that were aways treated with antibiotics are HSV2!!! The other is overexposure to Macrobid, which I took for many, many years for recurrent UTI’s. I have read all available literature, have followed your blog. It amazes me that the neurological consequences of HSV2 is not recognized except in acute cases. Please keep at it. and thank you.

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  6. -NoName says:

    Bill: I am completely disabled/homebound with bodywide small fiber neuropathy that spread like wildfire 2 year ago. The damage is done. I literally do not want to wake up anymore. I am in constant, level 10, suicidal pain. There are two culprits. I have HSV2 that I have KNOWN about but never treated since 2009 ( no known genital OB’s) ( now on daily valtrex). I learned this year that the huge outbreaks on my forehead that have been intermittent for a few years are HSV-2 !! They were being treated with antibiotics. The other culprit is Nitrofurantoin overexposure, which i have had a huge amount of over the years. On both fronts doctors think I am nuts. Meanwhile I no longer even drive. I am very, very sick with autonomic issues as well.

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  7. AB says:

    Dear Dr. Halford,

    First, and foremost, I would like to thank you for your dedication and relentless research on the HSV vaccine.

    I apologize if my question sounds stupid: once a person infected with HSV-2 gets treated with Theravax, will that person require a treatment with Profavax in order not to contract the virus again?

    Thank you for your consideration.

    Regards,
    AB

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    • Herpes Vaccine Research says:

      Dear AB,

      It is a reasonable question for a layperson who is not familiar with all the goals of a therapeutic HSV vaccine (e.g., RVx’s Theravax vaccine) and a prophylactic HSV vaccine (e.g., RVx’s Profavax vaccine).

      The primary difference between the two vaccines is purely a matter of virus dosage. Because prophylactic vs therapeutic HSV vaccines are still in development, it’s probably better to focus on some comparable vaccines that are currently used in practice like the VZV Oka virus (vaccine) that is used to prevent both chickenpox (primary infection with VZV) versus shingles (reactivation of latent VZV). The main difference between the chickenpox vaccine versus shingles vaccine is that the dose of VZV Oka virus is 13x greater in the shingles vaccine. This is because a child receiving the chickenpox vaccine as a 1-year-old has no immunity to VZV and so a low dose will suffice (cheaper to manufacture) and will make the vaccination a little milder for the recipient…but still strong enough to elicit a robust immune response. In contrast, with a 55-year-old who already had chickenpox as a kid, but is worried about getting shingles due to VZV reactivation, that person has pre-existing immunity to VZV and a 13-fold higher dose of VZV Oka is used to overcome the resistance provided by that pre-existing immunity to VZV.

      So, a therapeutic VZV vaccine (13x dose) is given to people who already have the VZV virus and some pre-existing immunity (i.e., VZV-specific antibody and VZV-specific T cells), whereas the preventative VZV vaccine (1x dose) is used in children or people who are immunologically naive to VZV because they have never had the chickenpox. The preventative vaccine’s lower dose is cheaper to manufacture and is likely better tolerated by VZV-naive individuals.

      The same would be true for Theravax (therapeutic HSV vaccine) versus Profavax (preventative HSV vaccine), but the details of dosage and delivery schedule remain to be determined until Phase 2 trials are under way.

      – Bill H.

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