We believe a properly attenuated live viral vaccine can be a game changer for the herpes pandemic.

Why the live viral vaccine approach?

“Live-attenuated vaccines against human viral diseases have been amongst the most successful and cost effective interventions in medical history.”1

“Live, replication-competent vaccines are more effective than replication-incompetent vaccines.”2

What does it mean for a biologic vaccine to be “live”?

A properly attenuated live viral vaccine must contain full antigenic breadth, must be able to replicate at the site of injection and infect new cells in the host. Without these basic properties, a biologic is not a live viral vaccine.

What constitutes properly attenuated in a biologic vaccine?

We believe a safe viral vaccine strain must be sufficiently active to go through at least several cycles of replication, but weakened enough so it can be effectively controlled by the host. We also believe the safest form of a properly attenuated live viral vaccine must be interferon sensitive.

Why live-attenuated viral vaccines are effective.

Live-attenuated viral vaccines are based on weakened (or attenuated) forms of viruses that cause disease. When a person is vaccinated with a properly attenuated live vaccine, the weakened virus mimics a wild-type infection at the site of injection without causing disease. This elicits a wide immune response that creates long-lasting protection. As a result, one or two doses of most live-attenuated viral vaccines can provide a lifetime of protection against an infectious pathogen and the disease it causes.3

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Why our approach is groundbreaking.

We are aiming to develop a properly attenuated HSV mutant as an immunotherapeutic.


Symptomatic herpectic disease is a condition of immuno-tolerance. Our theory is that by introducing a live-attenuated mutant of the herpes virus, which can safely replicate and infect new cells at the site of injection, our candidate may elicit a wide enough immune response so as to act as an immune modulator. Our hope is that this immunotherapy could help patients better control the symptoms caused by the reactivation of their wild type herpetic infection.

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How our approach is proprietary.

Our HSV vaccine candidates carry attenuating mutations in a key viral gene that encodes a protein named “infected cell protein 0” (ICP0). ICP0 controls the balance of HSV latency and replication. These mutations are designed to weaken the virus, limiting its ability to cause infection while retaining its ability to sufficiently stimulate the body’s immune system to elicit an effective and amplified response to combat infection.

ICP0 also aids the virus in evading the immune system’s protective defenses, namely the interferon-mediated response. Our patent protected vaccine candidates have a decreased ability to fight this immune response.

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Alternative vaccine approaches have limitations.

Subunit, inactivated (killed) and single cycle replication deficient viral vaccines by design may present an insufficient amount of the HSV virus’s protein to the immune system, which often limits the immune system’s capacity to elicit an adequate response against HSV-1 or HSV-2 infection. In contrast, live-attenuated viral vaccines enable a broad range of viral proteins to be expressed, which we believe may increase the likelihood of generating a robust and effective immune response.

Our pipeline.

We are developing multiple therapeutic and prophylactic HSV vaccine candidates. Our lead HSV-2 candidate, RVx-201, is designed to have a specific degree of attenuation through specifically designed mutations in the ICP0 protein.

Candidate
R&D
Pre-clinical
IND Enabling
Phase 1
Phase 2
Phase 3
BLA
RVx-201 HSV-2 Genital (Therapeutic)
RVx-101 HSV-1 Oral and Genital (Therapeutic)
RVx-202 HSV-2 (Prophylactic)
RVx-102 HSV-1 (Prophylactic)
RVx-301-COVID-19
RVx-302-COVID-19
RVx-VC2-HSV-1 (Prophylactic)

Research studies with the predecessor mutant of RVx-201 (termed in research publications HSV-2 0∆NLS) have provided the following observations:

  • Mice vaccinated with HSV-2 0∆NLS showed an improved antibody response compared to vaccination with a subunit vaccine candidate4
  • Mice immunized with HSV-2 0∆NLS were protected in subsequent challenges with live wild-type virus4
  • Studies in mice demonstrated the predecessor HSV-2 mutant to be avirulent,5 providing supportive evidence of its potential safety
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At present, Rational Vaccine’s pipeline is at an investigational, pre-clinical stage.

An approach proven effective in fighting the world’s most serious pandemic diseases

Rationally designed live-attenuated viral vaccines have significantly reduced or eliminated the spread of many devastating global pandemics throughout history and remain the most effective mode of vaccination today. The examples below demonstrate how they’ve helped to stop the spread of the most serious global pandemics in world history.6,7

1796 Smallpox

Smallpox was one of the world’s deadliest diseases for centuries, killing 3 out of 10 people it infected and leaving others scarred and blind. In 1796, Edward Jenner inoculated an 8-year-old boy with vaccinia virus (cowpox), observed that it created immunity from smallpox and went on to develop the first successful vaccine. His live-attenuated smallpox vaccine led to the eventual eradication of the disease worldwide in 1980 due to mass immunizations.

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1961 Polio

The first documented case of polio in the U.S. was in 1894 in Vermont, with 18 deaths reported. In 1916, it killed 2,000 people in New York City alone and 6,000 nationwide, leaving thousands more paralyzed. In 1952, 57,628 cases were reported. In 1961, the FDA approved a live-attenuated, oral polio vaccine developed by Dr. Albert Sabin that decreased worldwide incidence by 350,000 cases. By 2000, there was a 99% reduction in polio cases worldwide.

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1963 Measles

Measles is an easily transmitted airborne illness with fatal complications, including encephalitis. After the live-attenuated measles vaccine was licensed in 1963, over 19 million children were immunized in the U.S. over the next 12 years, leading to a 99% reduction of the disease. By 2000, the CDC declared measles eradicated in the U.S. due to highly effective vaccination programs. By 2015, the WHO declared measles was reduced to 134,000 deaths annually worldwide. Starting in 2017, outbreaks increased for two consecutive years due to gaps in vaccination coverage. Preliminary global data shows that reported cases were up 300% in the first three months of 2019 compared to the same period in 2018.8

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1969 Rubella

Also known as German measles, rubella causes a red rash and is a significant health risk to pregnant women. The last reported outbreak in 1964 infected 12.5 million people, including 50,000 pregnant women. It caused thousands of miscarriages, 20,000 cases of congenital rubella syndrome and 2,000 deaths. The first live-attenuated rubella vaccine was introduced in 1969, and by 2004 rubella was declared eliminated in the U.S.

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1995 Chicken pox

Chicken pox is a highly contagious, sometimes serious disease caused by the varicella-zoster virus. When the live-attenuated chicken pox vaccine was approved in 1995 by the FDA, the disease was impacting about 4 million people each year, leading to 10,000 hospitalizations and 1,000 deaths annually. By 2012, the CDC reported dramatically reduced death rates associated with chicken pox and 93% fewer hospitalizations due to chicken pox compared to before the vaccine.

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2006 Rotavirus

Rotaviruses are the most common cause of severe diarrheal disease and leading cause of gastroenteritis in young children worldwide. Prior to the introduction of the first attenuated live viral vaccines in 2006, each year more than 400,000 young children were seen by their physician for illness caused by rotavirus, with over 200,000 ER visits and 55–70,000 resulting hospitalizations in the U.S. Globally, rotavirus kills about 450,000 children under the age of 5 each year, with many of these deaths occurring in developing countries. Since recommended routine infant immunization in 2006, the CDC reports hospitalization rates for acute gastroenteritis dropped by 45% in 2008 compared to pre-vaccination (2000–2006), and it is estimated that the rotavirus vaccine prevented 55,000 hospitalizations in 2008. In Mexico, one of the first countries to receive the rotavirus vaccine in 2006, there was a reported 30% reduction in deaths from diarrheal disease in children ages 1–2 years old, and a 40% reduction in children younger than 11 months.6

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Eliminating Disease

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Eradicating Disease

We're committed to creating a world without herpes through rigorous research.