PRE-CLINICAL DEVELOPMENT OF NOVEL HSV-2 ANTIGENS

DESCRIPTION (provided by applicant): The objective of our proposed Phase II studies is to develop a vaccine for HSV-2 capable of eliciting human CD8+ and Th1-type CD4+ T cell responses for evaluation in humans. Prior clinical experience suggests that elicitation of immune responses other than neutralizing antibody in humans will be important to achieve a positive clinical effect. HSV-2 antigens will be selected for inclusion in our vaccine based on results of our Phase I studies on the prevalence of human T cell responses to HSV-2 antigens. The proposed Phase II studies will encompass construction and expression of a fusion-protein that will subsequently be formulated with Corixa's proprietary PLG-microspheres and adjuvants. The fusion-protein will be selected primarily based on its ability to sensitize APC for recognition by HSV-2 antigen-specific human T cells. Protein-microsphere formulations will subsequently be prepared, evaluated and further refined based on their immunogenicity in mice. Dosing and route-of-delivery studies will also be performed in mice to guide the design of Phase I clinical trials. On completion of the Phase II studies, a vaccine formulation capable of eliciting strong CD8+ and Th1-type CD4+ T cell responses will be selected for cGMP manufacturing and evaluation in humans in Phase I clinical trials.