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J Infect Dis. 2017 May 1;215(9):1376-1385. doi: 10.1093/infdis/jix086.

Higher T-Cell Responses Induced by DNA/rAd5 HIV-1 Preventive Vaccine Are Associated With Lower HIV-1 Infection Risk in an Efficacy Trial.

Author information

1
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and.
2
The Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington.
3
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
4
Emory Vaccine Center, Emory University, Atlanta, Georgia.
5
Laboratory of Infectious Disease Prevention, New York Blood Center, New York.
6
Departments of Medicine and Epidemiology/Biostatistics, University of California San Francisco.
7
University of Rochester Medical Center, School of Medicine and Dentistry, New York.
8
Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and.
9
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland; and.
10
Division of Infectious Diseases, Columbia University College of Physicians and Surgeons, New York.

Abstract

Background:

It is important to identify vaccine-induced immune responses that predict the preventative efficacy of a human immunodeficiency virus (HIV)-1 vaccine. We assessed T-cell response markers as correlates of risk in the HIV Vaccine Trials Network (HVTN) 505 HIV-1 vaccine efficacy trial.

Methods:

2504 participants were randomized to DNA/rAd5 vaccine or placebo, administered at weeks 0, 4, 8, and 24. Peripheral blood mononuclear cells were obtained at week 26 from all 25 primary endpoint vaccine cases and 125 matched vaccine controls, and stimulated with vaccine-insert-matched peptides. Primary variables were total HIV-1-specific CD4+ T-cell magnitude and Env-specific CD4+ polyfunctionality. Four secondary variables were also assessed. Immune responses were evaluated as predictors of HIV-1 infection among vaccinees using Cox proportional hazards models. Machine learning analyses identified immune response combinations best predicting HIV-1 infection.

Results:

We observed an unexpectedly strong inverse correlation between Env-specific CD8+ immune response magnitude and HIV-1 infection risk (hazard ratio [HR] = 0.18 per SD increment; P = .04) and between Env-specific CD8+ polyfunctionality and infection risk (HR = 0.34 per SD increment; P < .01).

Conclusions:

Further research is needed to determine if these immune responses are predictors of vaccine efficacy or markers of natural resistance to HIV-1 infection.

KEYWORDS:

HIV-1 vaccine; HVTN 505 vaccine efficacy trial; T-cell immunogenicity; T-cell polyfunctionality; correlates of risk; intracellular cytokine staining; machine learning analyses; vaccine-induced immune response.

PMID:
28199679
PMCID:
PMC5853653
DOI:
10.1093/infdis/jix086
[Indexed for MEDLINE]
Free PMC Article

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