The acquired immunodeficiency syndrome (AIDS) caused by HIV-1 is the leading cause of death inAfrica and the fourth leading cause of death worldwide. This IPCAVD is developing HIV/AIDS vaccinesthat use DMA for priming and MVA for boosting (DNA/MVA vaccine) as well as a simpler and ultimatelyeasier to deploy form of these vaccines, the use of MVA for both priming and boosting (MVA/MVAvaccine). 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. Inpreclinical studies, co-expression of GM-CSF has substantially enhanced protection. A centralhypothesis for the IPCAVD is that GM-CSF improves protection by enhancing the mucosal presence ofelicited T cell and Ab responses. Clade C HIV-1 which is endemic in southern Africa and parts of Asiaaccounts for about one half of the infections worldwide and >90% of the cases in India, a country with arapidly spreading infection that has surpassed South Africa in its total number of cases. The vaccinedevelopment effort of this IPCAVD is focused on developing a clade C vaccine for India.This manufacturing project has five specific aims: Vaccine vector development. Assessment of vaccine vectors for suitability for manufacture. cGMP contract manufacture and toxicology testing of vaccine vectors. Regulatory support for an HVTN phase 1 trial. 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 ofthe needed MVA vector will be by Dr. Bernard Moss under an Inter-Institutional Agreement for thedevelopment of DNA/MVA and MVA/MVA vaccines between GeoVax, Emory, CDC and the NIAID.