DNA/MVA IMMUNOGENS, CROSS-CLADE RESPONSES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This Program project has resulted in the taking of an HIV/AIDS vaccine into early phase human trials through the HIV Vaccine Trials Network (HVTN). The vaccine consists of priming with a recombinant DNA expressing HIV Gag, Pol, and Env proteins and then boosting with a recombinant MVA expressing the same proteins. The results of HVTN trial 45 (HVTN-045) showed the DNA component of the vaccine to be safe in humans. A 2nd phase 1 trial, HVTN-065 has now been initiated combining the DNA and MVA components of the vaccine. The low dose group (1/10th dose) was initiated in April 2006 and the full dose group in September of 2006. Both of these trials are still in progress. Both are showing the anticipated good safety for DNA/MVA. Ancillary assays being conducted under this Program Project suggest the elicitation of T cell responses in the majority of the low dose volunteers. Other studies supported by the project worked to characterize T cell responses in individuals infected with HIV/AIDS. These showed a deficit in IL-2 production in anti-HIV/AIDS CD8 and CD4 T cells in infected humans. This deficit was partially recovered during anti-viral drug treatment. Other studies also worked on the use of GM-CSF as an adjuvant for the DNA/MVA vaccine. GM-CSF was found to enhance the avidity maturation of the anti-Env Ab response. And finally, studies in mice tested how dose of the MVA immunogen affected immune responses and found that dose had a very limited effect on the height of the immune response.