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 an ultimately easier to deploy form of these vaccines, the use of MVA for both priming and boosting (MVA/MVA vaccine). Both the DNA 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 GMCSF 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 Project on preclinical studies and mucosal immune responses has five specific aims: ? Evaluation of the protective efficacy of co-expressed GM-CSF for DNA/MVA and MVA/MVA vaccines in the SIV251/rhesus macaque model ? Evaluation of the ability of co-expressed GM-CSF to enhance mucosal immune responses elicited by DNA/MVA and MVA/MVA vaccines. ? Evaluation of the effect of co-expressed GM-CSF on dendritic cell responses in DNA/MVA and MVA/MVA vaccinated macaques ? Conduct of a preclinical trial for the clinical product. ? Conduct of assays for human mucosal immune responses in the proposed human trial testing the GM-CSF concept. The Project is led by Dr. Rama Amara at the Emory Vaccine Center and the Yerkes National Primate Research Center
