Modification of the association between T-cell immune responses and human immunodeficiency virus type 1 infection risk by vaccine-induced antibody responses in …

Y Fong, X Shen, VC Ashley, A Deal… - The Journal of …, 2018 - academic.oup.com
Y Fong, X Shen, VC Ashley, A Deal, KE Seaton, C Yu, SP Grant, G Ferrari, AC deCamp…
The Journal of infectious diseases, 2018academic.oup.com
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 …
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.
Oxford University Press