RVx201 Herpes Vaccine Description 2022
RVx201 is a first-in-human herpes simplex virus type 2 (HSV-2) live-attenuated therapeutic vaccine modified to be interferon sensitive that destroys the ability of the virus to inhibit immune responses. Produced by Rational Vaccines, Inc., the technology is based on the pioneering research of the late Dr. William Halford, who dedicated over 25 years to studying herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2).
Rational's HSV vaccine candidates carry attenuating mutations in a critical 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. Unfortunately, ICP0 also aids the virus in evading the immune system's protective defenses, namely the interferon-mediated response.
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 candidate, Mice immunized with HSV-2 0∆NLS were protected in subsequent challenges with live wild-type virus, Studies in mice demonstrated the predecessor HSV-2 mutant to be avirulent, and providing supportive evidence of its potential safety.
The U.K. issued the Innovation Passport for RVx201 in July 2021. The Innovation Passport is awarded by the U.K.'s Innovative Licensing and Access Pathway Steering Group, consisting of the Medicines and Healthcare products Regulatory Agency (MHRA), National Institute for Health and Care Excellence, and the Scottish Medicines Consortium. RVx201 is the first vaccine for HSV-2 to be awarded this designation under ILAP, which the MHRA launched in January 2021.
On August 15, 2022, Rational Vaccines confirmed the observational clinical study, "A Study of the Characteristics of Patients Diagnosed With Recurrent Symptomatic Genital Herpetic Disease," with about 200 participants will be conducted at Southampton University Hospital and at Chelsea and Westminster Hospital, London, England.
No approved preventive vaccines, immunotherapies, or reliable treatments are currently available to cure herpes, says the WHO and the U.S. FDA.
Rational Vaccines, Inc. is located at 8 Cabot Rd #3800, Woburn, MA, with locations in Miami, FL, and Oxford, U.K.
RVx201 Indication
RVx201 Herpes Vaccine candidate is indicated to destroy the herpes virus (HSV-2) ability to inhibit immune responses. 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 injection site, our candidate may elicit a wide enough immune response 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,' says Rational Vaccines's website.
RVx201 Vaccine and HIV
People with compromised immune systems, such as those with advanced HIV infection, are impacted by herpes. According to the WHO, infections with HSV-1 and HSV-2 are common in patients infected with HIV. Patients may develop herpetic lesions at multiple sites, including the lips and oropharynx, genitalia, anus, fingers, and skin. This study aims to determine the frequency of such outbreaks in an HIV-positive population with recurrent HSV infection. Please contact Debra Barile at [email protected].
RVx201 Vaccine and Herpetic Keratitis
Original Research - Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration - published by Frontiers in Immunology on November 15, 2021 - provides proof of concept for the Company's HSV-1 vaccine candidate RVx201 to prevent herpetic keratitis - a leading infectious cause of blindness in developed countries.
Research results showed that RVX1001 administered prophylactically protected mice against lethal ocular HSV-1 challenge and the development of herpetic keratitis. Of note, study data showed that intramuscular vaccination of mice with RVX-1001 resulted in γδ (gamma delta) T cell enhanced accumulation and reduced infiltration neutrophils that substantially reduce HSV ocular immunopathogenesis. Of particular note, γδ T cells are a distinct group of T cells that straddle the innate and adaptive arms of the immune system and are involved in response to pathogens and tumors.
'Overall, our results strongly suggest that intramuscular immunization of mice with the live-attenuated VC2 vaccine strain significantly alters the infiltration of γδ T cells in the corneas of ocularly-challenged mice. Furthermore, these results suggest that a vaccine-generated tissue-specific memory response significantly protects against HSV-1 immunopathogenesis. The mechanism by which VC2-intramuscular immunization results in the observed tissue-specific response is currently under investigation.'
The work was supported by funds of the LSU Division of Biotechnology & Molecular Medicine, School of Veterinary Medicine, by a Governor's Biotechnology Initiative grant from the Louisiana Board of Regents (to K.K.), and by Cores of the Center for Experimental Infectious Disease Research, and Louisiana Biomedical Research Network, supported by NIH: NIGMS P30GM110670 and P20GM103424, respectively.
RVx201 News 2021 - 2022
August 15, 2022 - "Most people living with herpes are unaware they have the infection leading to unrecognized transmission and spread of the virus. Patients who develop symptomatic herpetic disease suffer not only from recurrent physical symptoms but may also suffer from social stigma and isolation because the infection is usually transmitted sexually," said Kerstin Westritschnig, M.D., chief medical officer of Rational Vaccines.
July 8, 2022 - Rational Vaccines announced findings from a U.S. National Institutes of Health (NIH)-funded pilot study of RVX201 that treatment led to a reduction in recurrent genital lesions when compared to gD2-alum/MPL vaccine or placebo in vivo. In addition, RVX201 appears to generate a robust cellular immune response equivalent to that elicited by wild-type HSV-2 on Day 7 post-infection. The study results also showed that in comparison to no vaccine, animals that received RVX201 had the number of symptomatic days reduced by 45%, while those that received the gD2-alum/MPL vaccine only had a 24% reduction in symptomatic days.
December 28, 2021 - Rational Vaccines announced preclinical research suggesting that the Company's herpes simplex virus type 1 (HSV-1) vaccine candidate (RVX1001) can protect against herpetic keratitis, a leading infectious cause of blindness in developed countries.
December 14, 2021 - Rational Vaccines announced the launch of a clinical trial designed to investigate the disease burden of HSV-1 and HSV-2 in patients with HIV infection. The study, "A 48 Week Observational Study of the Frequency of Symptomatic Herpes Virus I and II in HIV Infected Subjects," will be conducted at the Global Research Institute, located in Los Angeles, CA.
September 15, 2021 - Rational Vaccines announced Kerstin Westritschnig, M.D., as the Company's chief medical officer. Dr. Westritschnig brings extensive industry experience specializing in clinical immunology, including deep expertise in vaccine research and development, infectious disease, immune-oncology, and biologics.
July 22, 2021 - Rational Vaccines Receives UK MHRA Innovation Passport for RVx201 for the Treatment of Genital Herpes Resulting From Herpes Simplex Type 2 Virus. The United Kingdom's new Innovative Licensing and Access Pathway (ILAP) was launched by the U.K. Medicines and Healthcare products Regulatory Agency in January 2021 to reduce the time to market innovative medicines.
March 30, 2021 - A new study validated the preclinical safety of novel live-attenuated HSV-2 vaccine candidates.
RVx201 Clinical Trials
The 'Study of the Characteristics of Patients Diagnosed With Recurrent Symptomatic Genital Herpetic Disease - ClinicalTrials.gov Identifier: NCT05500053 was last updated on August 12, 2022. Being conducted by Solent NHS Trust, Southampton, U.K., United Kingdom, SO10 8BR.
In preclinical animal models, data have shown that RVx201 is safe and does not establish latency, and the vaccine's immunization protects against lethal challenges with virulent HSV-2 strains. Therefore, RVx201 is in the IND enabling stage of development.
