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 compared protective efficacy of 'prime-boost' immunization regimens using recombinant vaccinia virus (rVV) for priming and recombinant SIV proteins or inactivated SIV virions for boosting. Three groups of pig-tailed macaques (7/group) were primed with two rVV expressing SIVmne CL8 Env or Gag/Pol proteins and boosted a year later with recombinant gp160 and Gag/Pol virus-like particles in Alum/MPL adjuvant (Group 1), with adjuvant only (Group 2), or with 2,2'-dithiodipyridine (aldrithiol-2)-inactivated SIVmne (AT-2 SIV) (Group 3). Four weeks later, all animals were challenged intravenously with an uncloned SIVmne. While all animals were infected after challenge, immunized animals had significantly reduced plasma viremia compared with controls. Reduction of viremia correlated with high levels of vaccine-induced SIV antibody and IFN-gamma ELISPOT responses at challenge. To gain further insight into the protective mechanism, we analyzed nucleotide sequences in the envelope region of the uncloned challenge virus and compared them with those present in the PBMC of infected animals collected between 2-4 weeks after challenge. Approximately 50% of the V1 sequences from the uncloned challenge virus was identical to the molecular clone CL8 from which the vaccines were made (CL8 type), with the remainder containing several conserved changes (variant type). Na ve control animals infected with this uncloned virus had both types of V1 sequences in varying proportions, the mean of which (38.4% of CL8 and 61.6 % of variant type) is similar to that in the challenge stock. On the other hand, 16/17 immunized animals analyzed had predominantly (96.6 +/- 8.3 %) the variant type V1 sequence early after infection. These results support our earlier findings, indicating that the protective immunity elicited is primarily restricted to the homologous virus and that immune responses directed to the V1 region of the envelope protein may play a role in protection.
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