Dendritic Cell-Targeted HIV Vaccine Product

DESCRIPTION (provided by applicant): This proposal is a unique collaboration between a small, but full capability, Biotechnology Company and a premier academic institution and laboratory to develop a novel product for clinical trials in cancer patients. The project provides for additional employment and economic growth benefits through the development plan, and has the potential to have significant economic benefit if the treatment becomes successful. This proposal describes a vaccine product aimed toprovide a feasible and nontoxic way to elicit strong immunity in humans to HIV proteins, and it will provide an added arm to vaccine strategies such as recombinant viral vectors. The technology behind this product is based on our most recent understandingof immunology and vaccines. First, the product ensures for the first time that HIV envelope and gag antigens are efficiently targeted to antigen presenting dendritic cells by using recombinant antibody technology. This vaccine product uses a human monoclonal antibody, generated by the PI's, that can seek out and bind to the subject's dendritic cells expressing the molecule DEC-205. In this way, a large number of dendritic cells in lymphoid organs can present antigens to rare antigen-specific T cells and efficiently initiate the immune attack against HIV proteins. Second, the product includes a stimulus or adjuvant that results in a strong innate response, which in turn is required for the optimum immune response. This product encompasses proprietary immune activators with clinical and pre-clinical track record. Importantly, these agents have been secured for use in these products through licensing partnerships and agreements. Finally, the product has carefully selected specific HIV envelope andgag antigens. These antigens individually have documented immunogenicity in mice and monkeys, when delivered to DEC-205, and now need to be combined into a vaccine product suitable for further development in phase II in mice and monkeys. PUBLIC HEALTH RELEVANCE: Dendritic cells are critical for the initiation of immunity. This proposal will harness the capacities of dendritic cells to initiate antibody and cell-mediated immunity against HIV. In the phase I portion, we will produce an antibody that efficiently delivers two HIV proteins to dendritic cells, and we will carry out proof of concept for improved immunity by giving vaccine together with safe adjuvants or immune enhancers to humanized mice. This proposal therefore describes an innovative product that addresses the need to be able to use proteins in an effective and nontoxic way to elicit and boost immunity against HIV, offering the potential of considerable impact in our country and worldwide.