In this post, I address three questions about RVx’s new line of highly effective HSV-2 vaccines:
- Why do we need an effective HSV-2 vaccine ASAP?
- What makes RVx’s HSV-2 vaccines more effective?
- How would an effective HSV-2 vaccine change the future?
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:
- A therapeutic HSV-2 vaccine that may provide a new treatment option to those who currently live with chronic, unrelieved disease; and
- 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.
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:
Furthermore, the literature on the safety and superiority of live HSV-2 ICP0‾ mutant vaccines may be found in these reviews:
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 firstname.lastname@example.org 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 email@example.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.