Trivalent Adenovirus Type 5 HIV Recombinant Vaccine Primes for Modest Cytotoxic Capacity That Is Greatest in Humans with Protective HLA Class I Alleles
Figure 3
The HIV-specific CD8+ T-cells of Ad5/HIV vaccinees exhibited per-cell cytotoxic capacity that was significantly lower than that of LTNP but only somewhat higher than that of progressors.
Cytotoxic responses mediated by day 6 CD8+ T-cells were measured by ICE for all individuals at a standard E:T ratio of 25∶1 or an increased E:T ratio of 50∶1 (total day 6 CD8+ T-cells to total CD4+ T-cell targets) and subsequently plotted against the true E:T ratios based on measurements of IFN-γ-secreting CD8+ T-cells and p24-expressing target cells, respectively. Curves represent trends for responses of LTNP (n = 18, red), viremic progressors (n = 19, blue), Ad5/HIV vaccinees measured at the standard E:T ratio of 25∶1 (n = 31, open green) and a subset of Ad5/HIV vaccinees also measured at an increased E:T ratio of 50∶1 (n = 20, open black). Regression analysis, analysis of covariance and repeated measures were used to quantify the differences in ICE among LTNP, progressors and Ad5/HIV vaccinees over the range of logged E:T ratios, at the median log E:T ratio of the combined groups and at the log E:T ratio of 5∶1. ICE of LTNP differed by constant amounts from that of vaccinees over the shared range of true E:T ratios measured with either standard (p<0.001) or increased (p<0.001) numbers of CD8+ T-cells. However, the differences between progressor and vaccinee ICE trend lines at standard (p = 0.02) and increased (p = 0.05) numbers of CD8+ T-cells depended on the value of the E:T ratio over the shared range. See text for more details.