Research Project
8319629
The acquired immunodeficiency syndrome (AIDS) caused by HIV-1 is the leading cause of death in Africa and the fourth leading cause of death worldwide. This IPCAVD is developing HIV/AIDS vaccines that use DMA for priming and MVA for boosting (DNA/MVA vaccine) as well as a simpler and ultimately easier to deploy form of these vaccines, the use of MVA for both priming and boosting (MVA/MVA vaccine). Both the DMA and MVA vaccines use single vectors to express virus like particles (VLP). This IPCAVD seeks to build GM-CSF, an adjuvant, into these products for expression in cis. In preclinical studies, co-expression of GM-CSF has substantially enhanced protection. A central hypothesis for the IPCAVD is that GM-CSF improves protection by enhancing the mucosal presence of elicited T cell and Ab responses. Clade C HIV-1 which is endemic in southern Africa and parts of Asia accounts for about one half of the infections worldwide and >90% of the cases in India, a country with a rapidly spreading infection that has surpassed South Africa in its total number of cases. The vaccine development effort of this IPCAVD is focused on developing a clade C vaccine for India. This manufacturing project has five specific aims: [unreadable] Vaccine vector development. [unreadable] Assessment of vaccine vectors for suitability for manufacture. [unreadable] cGMP contract manufacture and toxicology testing of vaccine vectors. [unreadable] Regulatory support for an HVTN phase 1 trial. [unreadable] Development and conduct of release and stability assays. The project will be led by Dr. Mark Keister and co-directed by Dr. Harriet Robinson. Construction of the needed MVA vector will be by Dr. Bernard Moss under an Inter-Institutional Agreement for the development of DNA/MVA and MVA/MVA vaccines between GeoVax, Emory, CDC and the NIAID.
