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J Infect Dis. 2018 Mar 28;217(8):1280-1288. doi: 10.1093/infdis/jiy008.

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.

Author information

1
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle.
2
Department of Biostatistics, University of Washington, Seattle.
3
Duke Human Vaccine Institute, Duke University, Durham, North Carolina.
4
Department of Medicine, Duke University, Durham, North Carolina.
5
Department of Surgery, Duke University, Durham, North Carolina.
6
Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina.
7
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryl.
8
Department of Immunology, Duke University, Durham, North Carolina.
9
Division of Infectious Diseases, Department of Medicine, Columbia University, New York, New York.
10
Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryl.
11
Orlando Immunology Center, Florida.
12
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
13
School of Medicine, University of Pennsylvania, Philadelphia.
14
Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco.
15
Division of Infectious Diseases, University of Illinois at Chicago.
16
Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee.
17
University of Rochester Medical Center, Rochester, New York.

Abstract

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.

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