Biomedical Research Models, Inc. — Department of Health and Human Services SBIR Phase I: R

Description

Globally an estimated of the human population is infected with HSV including andgt of the U S adult population Genital herpes is associated with an increased risk of HIV acquisition and transmission of HSV infection can cause neonatal herpes with high infant mortality HSV infection in the adult population has increased substantially in the past two decades despite the availability of antiviral drugs The failure of antiviral drugs to prevent the spread of HSV and the sheer magnitude of the public health problem associated with HSV infection indicates a need for a safe and effective vaccine that is not available As to the protective mechanism the current consensus of HSV experts is that serum antibody response alone is insufficient to provide protective immunity primarily based on the disappointing clinical trial results Therefore mucosal immunity and T cell responses are considered very important HSV is a very unique virus able to escape from immune surveillance and inhibit immune responses in order to successfully infect the host and establish latency With NIAID SBIR phase I and II grant funding we made a significant finding that HSV infected Guinea Pigs GP untreated or provided with a reference vaccine that mimics the HSV vaccine which failed in latest clinical trial were unable to elicit vaginal IgA Unlike other HSV vaccine candidates our mucosal vaccine technology employs a patented heterologous prime boost strategy consisting of a DNA vaccine prime given intramuscularly i m and a protein encapsulated liposome vaccine boost delivered intranasally i n This two step heterologous immunization strategy developed as a mucosal vaccine regimen provides a multi tiered protection with a Th biased broad and potent cellular and humoral immune response especially mucosal immune response and vaginal protection against primary and latent HSV infection This novel HSV vaccine shows both prophylactic and therapeutic efficacies particularly at the genital site of the guinea pig models The company was recently funded by a phase IIB SBIR grant for our HSV vaccine to support cGMP manufacturing of key vaccine components towards the ultimate goal of IND filing and clinical trials This new phase I R SBIR grant application was developed in response to the Study Sectionandapos s suggestion of strengthening studies on nasal delivery devices We plan to conduct bio distribution bioavailability studies comparing nasal spray vs nasal drop delivered HSV gD Liposome vaccine in New Zealand White rabbits We also propose to compare the immunogenicity and immune protection efficacies of gD lip formulation delivered by nasal drop vs nasal spray in female GPs that will be first primed with our HSV DNA vaccine If funded it would help fill in the gap in the critical pathway of advancing our mucosal HSV vaccine candidate to clinical trials The net result of these research efforts will be to identify a more efficient nasal delivery device for our mucosal HSV vaccine and ultimately alleviate pain risk and suffering in the million Americans with genital Herpes Project Narrative Evaluation of the bio distribution and protective efficacy of a mucosal HSV vaccine delivered in animal models by nasal spray vs nasal drop is a critical step for selection of one of them for GMP filling of the mucosal HSV vaccine GLP toxicology study and Pre IND meeting Data from this proposal will fill in a significant gap in the critical pathway of advancing this novel vaccine to clinical trials Success of this study will clearly have an impact on the greater than $ billion spent annually on direct medical costs associated with HSV The Public Health Service PHS has recognized the significant public health issues caused by herpes simplex virus The PHS publication andquot Healthy People andquot has set sexually transmitted diseases as a national priority with a goal to reduce the number of adults infected with human papilloma virus and HSV