Development of Recombinant SARS VLP Vaccines

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DESCRIPTION (provided by applicant): The objective of this grant proposal is to develop and manufacture preclinical and clinical lots of novel recombinant SARS subunit protein vaccines formulated with Novasome adjuvants for evaluation in small animal and primate challenge models to prevent SARS coronavirus infection and disease. This plan will develop three types of SARS vaccine candidates comprised of recombinant SARS coronavirus S, M, and E proteins, which have been codon-optimized, cloned, and expressed in baculovirus-infected insect cells at Novavax, Inc. Vaccine candidates include the following: (1) recombinant multiprotein immunogens displayed on Novasomes, (2) VLPs self-assembled in vivo, and (3) chimeric VLPs comprised of SARS viral proteins and human influenza virus hemagglutinin proteins. Vaccine immunogens, expressed in baculovirus-infected insect cells and/or CHO cells, will be purified by ultracentrifugation and chromatographic methods. Vaccine immunogens will be formulated with adjuvants and will be evaluated initially for mucosal and systemic immunogenicity in mice. Vaccine candidates that elicit SARS neutralizing antibodies in the murine immunogenicity model, as determined by microneutralization assays, will be evaluated further in a novel SARS mouse challenge model in collaboration with Dr. Kanta Subbarao (NIH), who recently developed the model. Preclinical lots of vaccine candidates that elicit neutralizing antibodies and reduce virus titers in the murine challenge model will be tested further in a SARS primate challenge model using cynomolgus monkeys in collaboration with Dr. James Estep (Battelle Institute) in their BSL3 primate facility. Finally, clinical lots of a SARS vaccine candidate that demonstrates the highest SARS neutralizing antibody titer and the greatest virus reduction in the primate challenge model will be manufactured and lot release tested. Toxicology studies of the SARS vaccine candidate will be conducted in rabbits. A clinical protocol for a Phase I clinical study will be prepared, and an IND application will be submitted to CBER/FDA.