Enhancing Malaria Vaccine Development by the Navy Medical Research Center

"The goal of the Phase II project will be to optimize a PLGA form for clinical trials based on characterization of the dose/response of the particulate in small and large animal models. The particular challenge in moving a DNA/PLGA formulation through thepreclinical stages to clinical trials lies in the translation of dose/response information from a very small animal model (rodent) to a larger animal model (primate). However, the attractive of particulate PLGA dose forms is based on their capacity toelicit immune responses based on their long-term persistence in the neighborhood of antigen presenting cells. Therein lies the thrust of optimization for vaccine efficacy-titration of the dose/response behavior of PLGA particulates. Phase II work will utilize the team structure established in Phase I. NMRC will produce and purify a candidate DNA plasmid for supply to Cambridge Scientific, Inc. (CSI). CSI will produce and characterize DNA/PLGA vaccines under Good LaboratoryPractices (GLP). CSI will fully characterize the dose forms based on plasmid loading, release, and integrity. CSI will optimize the dose/response in mice, then demonstrate immunogenicity and in some cases protective efficacy in non-human primates. Theworkplan will be carried out under strict documentation clauses so that the candidate DNA/PLGA formulation can be finalized in a prototype system that can be transitioned to clinical testing in Phase III and eventual com