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.

Journal Article (Clinical Trial;Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Fong, Y; Shen, X; Ashley, VC; Deal, A; Seaton, KE; Yu, C; Grant, SP; Ferrari, G; deCamp, AC; Bailer, RT; Koup, RA; Montefiori, D; Haynes, BF; Sarzotti-Kelsoe, M; Graham, BS; Carpp, LN; Hammer, SM; Sobieszczyk, M; Karuna, S; Swann, E; DeJesus, E; Mulligan, M; Frank, I; Buchbinder, S; Novak, RM; McElrath, MJ; Kalams, S; Keefer, M; Frahm, NA; Janes, HE; Gilbert, PB; Tomaras, GD

Published Date

  • March 28, 2018

Published In

Volume / Issue

  • 217 / 8

Start / End Page

  • 1280 - 1288

PubMed ID

  • 29325070

Pubmed Central ID

  • PMC6018910

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

Digital Object Identifier (DOI)

  • 10.1093/infdis/jiy008


  • eng

Conference Location

  • United States