Research Project
6211453
The objective of this study is to provide pre-clinical data for the development of a vaccine for HSV-2 in humans. Using expression- cloning technology, we have identified antigens that can be recognized by HSV-2-specific helper (CD4+) and cytotoxic (CD8+) T cells from HSV-2 seropositive donors: 5 antigens for CD4+ T cells, 2 for CD8+ T cells. No detailed immunologic studies have yet been performed on these antigens. This study proposes to perform detailed pre-clinical analysis prior to selection of antigens for vaccine formulation. CD4+ and CD8+ T cells from human donors whose clinical and serological status is known will be tested for recognition of these antigens. T cell responses will be correlated with HSV-2 disease in a dichotomous clinical severity model. Antigens for which strong T cell responses of the appropriate phenotype are associated with few annual HSV-2 recurrences will be formulated with Corixa's proprietary adjuvants and tested for immunogenicity in mice. Formulations eliciting immunogenic responses in mice will be tested for protection in a murine model of HSV-2 disease. SBIR Phase II studies will evaluate the vaccine's safety and its ability to elicit appropriate immune responses in human subjects in Phase I clinical trials. PROPOSED COMMERCIAL APPLICATIONS: The vaccine developed as a result of this study and future clinical studies will be used for treatment of HSV-2 disease in humans. An estimated 22% (> 18 million persons) of the United States population currently have with HSV-2 and the rate of new HSV-2 infections has been estimated at 500,000 per year. The incidence of neonatal herpes is currently estimated at about 113,000-10,000 live births per year and the infection is frequently lethal. The prevalence of HSV-2 infection has increased substantially in the past two decades, despite the availability of anti-viral drugs, such as acyclovir, to treat the disease. Treatment of primary viral infection with anti-viral drugs can successfully diminish the severity and duration of clinical symptoms, but cannot prevent establishment of latent infection. Long-term anti-viral drug therapy can have compliance problems. The magnitude of the public health problem posed by HSV-2, and the failure of antiviral drugs to prevent its spread, points to a clear need for a safe and effective vaccine for HSV-2.
