An explosion in knowledge related to HIV vaccine research has led to the concept of B cell lineage immunogen design as an HIV vaccine strategy. In this strategy, broadly neutralizing antibody (bnAb) B cell lineages are determined in HIV-infected individuals, and then sequential immunizations are designed to recapitulate, with a multi-component vaccine, the immunologic events that transpire during bnAb development in infection. However, a major bottleneck in developing this strategy and advancing it to clinical trials is a bottleneck in production of clinical trial materials to test these vaccines. In particular, greater capacity is needed to produce clinical trial materials under Current Good Manufacturing Practices (CGMP) in an environment that also has HIV vaccine expertise. To begin addressing this bottleneck, earlier this year the Duke Human Vaccine Institute (DHVI) ? a leader in HIV vaccine development efforts ? and the Duke University School of Medicine opened a 1,600 net. sq. ft. CGMP manufacturing facility which can produce at most two HIV vaccine-related proteins for clinical trial use per year. Because recent studies in animals suggest that an effective HIV vaccine may require as many as 10 different proteins and may benefit from inclusion of specific RNA and/or DNA, additional capacity for protein production and new capabilities for RNA and DNA production are needed. Thus we propose to upgrade existing functional space to create an additional 2,500 net sq.ft CGMP facility at Duke. This new facility will expand our protein production capacity, enable manufacturing of CGMP-grade RNA and/or DNA, and do so in an efficient and expert manner. The overall objective of this grant is to design and build a CGMP facility at Duke to enhance our capacity to produce clinical trials materials, have the capacity to produce recombinant proteins, mRNA or DNA immunogens, and capitalize on the unique expertise of the DHVI team in HIV vaccine immunogen design and CGMP production. Because of our team's involvement with international HIV vaccine research and development efforts, this facility will be connected to clinical trial needs and will help accelerate the effort to develop, test, and make available an effective HIV vaccine.
