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 to prevent HIV infection. This proposal describes a vaccine product aimed to provide a feasible and nontoxic way to elicit strong immunity in humans to HIV proteins, and it will provide an added arm to be combined vaccine strategies such as recombinant viral vectors. The technology behind this product is based on our most recent understanding of 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, which 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 agains 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 activator with clinical and pre-clinical track record. Finally, the product has carefully selected specific HIV envelope and gag antigens, and has demonstrated feasibility of manufacturing and proof of concept in our Phase I program. This project will now be focused on further demonstrating the value of a prime boost approach with a viral vector vaccine, and manufacturing product for human use and other studies that will support a clinical trial in healthy volunteers for assessing the potential of the vaccine to preven HIV infection.
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 produced an antibody that efficiently delivers two HIV proteins to dendritic cells, and showed proof of concept for improved immunity by giving vaccine together with safe adjuvants to mice. In the Phase 2 portion, we will confirm the increaded immunogenicity of a prime boost approach with a viral vector HIV vaccine and also make the product ready for clinical testing by conducting GMP manufacturing and performing the safety and animal studies to support the Investigational New Drug (IND) application. 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.