COMBINATION VACCINE/MICROBICIDE EFFICACY ASSESSMENT IN THE SHIV/MACAQUE MODEL

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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. We completed repeat IVAG challenge of the eight DNA/Ad5 SIV gag-pol vaccinated and eight unvaccinated female Indian rhesus macaques (RM). We modified the challenge protocol as follows to assure that 100% of the unvaccinated macaques will be infected: 10 challenges with 300 TCID50, 5 challenges with 1000 TCID50 and 5 challenges with 3000 TCID50 of cell-free SHIVSF162P3 for a total of 20 exposures. Using this escalated dose challenge protocol, all 8 macaques in the control unvaccinated group were infected, with a range of 3-18 exposures needed to establish systemic infection. Six of the eight vaccinated macaques were also infected, with 1-17 inoculations needed for infection, while two remained uninfected after 20 exposures. Analysis of the cumulative proportion of uninfected macaques as a function of the number of weekly intravaginal exposures showed that the survival curve for the vaccinated group shifted to the left of the control curve from the 1st to 3rd exposure, reflecting the fact that two of the vaccinated macaques were infected after 1 and 2 virus exposures, whereas a minimum of three exposures was required to infect animals in the unvaccinated group. The vaccine survival curve diverged from that of the control after the 5th exposure, becoming maximal from the 9th to the 16th exposure. This latter observation, together with the fact the 2 of the 8 vaccinated macaques remained uninfected after 20 challenges is suggestive of a "leaky vaccine" effect.