IMMUNOGENICITY IN MACAQUES OF A DNA/OLIGOMERIC ENVELOPE PROTEIN HIV VACCINE

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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 study was designed to evaluate clinical-grade DNA formulated with poly(lactide-coglycolide) (PLG) microparticles and clinical-grade, recombinant Env protein vaccines for HIV using a DNA/PLG prime ' protein boost regimen. A secondary goal of the study was to compare the immune responses of M. mulatta and M. fascicularis. Macaques were vaccinated at weeks 0, 4, and 8 with plasmid DNAs expressing HIV-1 gag and env. Plasmids were formulated with cationic PLG microparticles. Booster vaccinations with recombinant HIV gp140env protein mixed with an equal volume of MF-59 adjuvant were given intramuscularly at weeks 24, 36 and 48. Animals were bled periodically and immune function assays performed. Env- and gag-specific plasma IgG titers were measured by ELISA. Two fascicularis seroconverted to gag, but none of the mulatta had positive titers. All animals developed positive env titers after one protein boost and remained positive throughout the 59-week study. Titers for the two species were similar. All sera obtained after the second env protein vaccination were positive for HIV neutralizing antibodies with mulatta and fascicularis having comparable titers. Env- and gag-specific CD4+ and CD8+ T cells were quantified by cytokine flow cytometry (CFC). CD4+ T-cell gag-specific responses were detected only at one time point in 1 mulatta and 1 fascicularis. No env-specific CD4+ T-cell responses were detected during the DNA/PLG priming phase. After the third protein boost, however, all 6 mulatta but only 1 fascicularis had positive CD4+ responses. CD8+ T-cell responses were low in both species with gag-specific responses peaking at two weeks after the third DNA/PLG immunization env-specific responses after 3 protein boosts. To investigate the differences observed between the species? CD4+ T-cell responses, this study was extended to examine whether CD4+CD25+ regulatory T cells suppressed the antigen-specific T-cell responses in M. fascicularis. Our results indicated that probably this was not the case.