“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
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.
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.
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
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.
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.
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.
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.
Research studies with the predecessor mutant of RVx-201 (termed in research publications HSV-2 0∆NLS) have provided the following observations:
At present, Rational Vaccine’s pipeline is at an investigational, pre-clinical stage.
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
