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. The goal of our studies is to test potential vaccine and adjuvant formulations for safety and immunogenicity in the nasal cavity. In particular, we are seeking products that produce strong HIV-specific immune responses in the female genital tract and rectum, mucosal tissues which serve as major HIV reservoirs after infection. Vaccines which induce antiviral responses at these sites should be more effective than current intramuscular vaccines which primarily induce responses in nonmucosal compartments. We have previously shown that the nasal vaccination route is best for producing immune responses in both the female genital tract and rectum. However, adjuvants which could be used to enhance immune responses to HIV nasal vaccines have not yet been identified for humans. In this past year, we tested the safety and adjuvanticity of a potential nasal adjuvant, the QS-21 saponin derivative. Nasal co-administration of 10 or 25 ug QS-21 with a recombinant HIV gp41 protein in rhesus macaques did not produce any local or systemic adverse reactions. In addition, animals nasally vaccinated with gp41 plus 25 ug QS-21 developed significantly greater proportions of gp41-specific IFN-gamma- and IL-2-secreting CD8 and CD4 T cells in blood and vaginal mucosa when compared to animals vaccinated with gp41 alone. The ability of QS-21 to augment mucosal responses to nasal HIV DNA vaccines will next be tested. These studies should facilitate the development of vaccines which prevent HIV infection.
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