Although an effective vaccine must elicit high levels of broad HIV-1 specific neutralizing antibodies, CTLs and helper T cell response, none of these immune parameters has been shown to control virus replication and prevent the development of disease in a consistent manner. Therefore, it is necessary to search for other immune markers that may be correlated with protection. Recently, some studies have shown that protection in SIV vaccinated monkeys are correlated with CD8+ cell suppressive activity against SIV, but not with CTL or virus neutralizing antibody. The hypothesis is that CD8 suppressive activity is correlated with protection against challenge virus. The overall objective of this project is to develop a high throughput CD8 suppression assay with fresh and frozen cells, and to determine whether the level of this antiviral activity is increased following immunization in humans and correlated with protection against challenge virus in the SIV/Macaque model.
Specific aims of the project are 1) to develop a high through put quantitative CD8 suppression assay for HIV-1 and SIV. The present assay format will be miniaturized such that it would require small numbers of cells and be performed rapidly in fresh and frozen cells. 2) To determine whether CD8 suppression of SIV, like that of HIV-1, is dependent on phenotypic properties of SIV. 3) To evaluate longitudinally the level of CD8 suppressive activity against the immunizing strain of HIV-1 and CCR5 tropic HIV-1 in vaccinated humans enrolled in the AVEG studies. 4) To evaluate longitudinally the level of CD8 suppressive activity against the immunizing and challenge strain of SIV in vaccinated monkeys and to determine whether its level is correlated with protection in the NCVDG study. The information generated from this project will be extremely useful in determining the utility of the suppressive activity in evaluating efficacy of a vaccine.
