Clinical Trials and Ancillary Assays

点击翻译按钮获取中文摘要

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 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 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 clinical studies project has four specific aims: ¿ Provide support for phase 1 b of HVTN-065, an ongoing clinical trial testing clade B DNA/MVA and MVA/MVA regimens for safety and immunogenicity. ¿ Conduct ancillary immunogenicity assays for the phase 1 b portion of HVTN 065 ¿ Provide specimens from human volunteers for development of mucosal assays ¿ Submit the concept sheet and help with protocol development for an HVTN trial assessing the clade C vaccines in the presence and absence of GM-CSF expression in cis ¿ Conduct ancillary immunogenicity assays for the HVTN clade C vaccine trial Dr. Mark Mulligan, an experienced clinical trials investigator, will lead the HVTN interface for the project at Emory. Dr. Harriet Robinson will serve as co-P.I. and oversee the conduct of ancillary assays on fresh cells in a dedicated GLP lab at GeoVax.