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COMBINED APPROACH TO BROADLY PROTECTIVE AIDS VACCINES: PROJECT 4

$465,257P51FY2010RRNIH

University Of Washington, Seattle WA

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Abstract

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 previously reported comparative studies of the protective efficacy of different "prime-boost" immunization regimens consisted of priming with recombinant vaccinia or DNA vectors expressing HIV-1 SF162 Env or SIVmac239 Gag/Pol, followed by boosting with DNA, protein;or heterologous viral vector expressing the same antigens. Results showed that, regardless of the priming immunogen, animals boosted with protein vaccines had significantly higher antibody titers, including homologous neutralization antibodies (NtAb). After SHIVSF162P4 challenge, significant reduction of mean plasma viral load was observed in all immunization groups. An inverse correlation (Spearman's r = -0.819), p10-fold less than those achieved by animals that were primed DNA or virus vector vaccines. Following intrarectal SHIV162 P4 challenge, all but one animal in each of the protein-DNA or protein-protein prime-boost groups were infected. These results further support the important role of priming in the prime-boost immunization in the generation of protective immunity against primate lentivirus infection.

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