Modification Of The Association Between T-Cell Immune Responses And Human Immunodeficiency Virus Type 1 Infection Risk By Vaccine-Induced Antibody Responses In The Hvtn 505 Trial

Background. HVTN 505 was a human immunodeficiency virus type 1 (HIV-1) preventive vaccine efficacy trial of a DNA/ recombinant adenovirus serotype 5 (rAd5) vaccine regimen. We assessed antibody responses measured 1 month after final vaccination (month 7) as correlates of HIV-1 acquisition risk.Methods. Binding antibody responses were quantified in serum samples from 25 primary endpoint vaccine cases (diagnosed with HIV-1 infection between month 7 and month 24) and 125 randomly sampled frequency-matched vaccine controls (HIV-1 negative at month 24). We prespecified for a primary analysis tier 6 antibody response biomarkers that measure immunoglobulin G (IgG) and immunoglobulin A (IgA) binding to Env proteins and 2 previously assessed T-cell response biomarkers.Results. Envelope-specific IgG responses were significantly correlated with decreased HIV-1 risk. Moreover, the interaction of IgG responses and Env-specific CD8(+) T-cell polyfunctionality score had a highly significant association with HIV-1 risk after adjustment for multiple comparisons.Conclusions. Vaccinees with higher levels of Env IgG have significantly decreased HIV-1 risk when CD8(+) T-cell responses are low. Moreover, vaccinees with high CD8(+) T-cell responses generally have low risk, and those with low CD8(+) T-cell and low Env antibody responses have high risk. These findings suggest the critical importance of inducing a robust IgG Env response when the CD8(+) T-cell response is low.