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. Both the DNA and MVA express Virus Like Particles. A low dose group (n=10) received 0.3 mg JS7 DNA at months 0 and 2, and 107 TCID50 of MVA62 at months 4 and 6. A high dose group (n=30) received 3 mg of JS7 DNA and 108 TCID50 of MVA62 at the same intervals. Placebos received saline (n=8). All inoculations were intramuscular. Both the low and high doses of the vaccine have been well tolerated and immunogenic in humans. Following the 2nd MVA immunization, 77% (20/26) of the high dose, 87% (7/8) of the low dose and none (0/8) of the placebo recipients had responding CD4 T cells; and 42% (11/26) of the high dose, 33% (3/9) of the low dose, and none (0/8) of the placebos had responding CD8 T cells. Responses were targeted to Gag~EnvPol. In contrast to the T cell responses, Ab responses increased with vaccine dose. Following the 2nd MVA inoculation, 88% of the high dose, but only 22%, of the low dose group had anti-Env binding Ab. The 2nd MVA increased the CD8 and Ab responses but not the CD4 responses.