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J Infect Dis. 2016 Feb 15;213(4):541-50. doi: 10.1093/infdis/jiv496. Epub 2015 Oct 15.

Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083.

Author information

1
Division of Infectious Diseases, Brigham and Women's Hospital Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, Massachusetts.
2
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
3
Division of Infectious Diseases, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts.
4
Columbia University, New York.
5
San Francisco Department of Public Health, California.
6
Vanderbilt University School of Medicine, Nashville, Tennessee.
7
University of Alabama, Birmingham.
8
Emory University, Decatur, Georgia.
9
University of Rochester, New York.
10
Division of AIDS.
11
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center Department of Global Health, University of Washington, Seattle.
12
Duke Human Vaccine Institute, Duke University, Durham, North Carolina.
13
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center Department of Global Health, University of Washington, Seattle Departments of Medicine and Laboratory Medicine, University of Washington, Seattle.
14
Dale and Betty Bumpers Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.

Abstract

BACKGROUND:

Increasing the breadth of human immunodeficiency virus type 1 (HIV-1) vaccine-elicited immune responses or targeting conserved regions may improve coverage of circulating strains. HIV Vaccine Trials Network 083 tested whether cellular immune responses with these features are induced by prime-boost strategies, using heterologous vectors, heterologous inserts, or a combination of both.

METHODS:

A total of 180 participants were randomly assigned to receive combinations of adenovirus vectors (Ad5 or Ad35) and HIV-1 envelope (Env) gene inserts (clade A or B) in a prime-boost regimen.

RESULTS:

T-cell responses to heterologous and homologous insert regimens targeted a similar number of epitopes (ratio of means, 1.0; 95% confidence interval [CI], .6-1.6; P = .91), but heterologous insert regimens induced significantly more epitopes that were shared between EnvA and EnvB than homologous insert regimens (ratio of means, 2.7; 95% CI, 1.2-5.7; P = .01). Participants in the heterologous versus homologous insert groups had T-cell responses that targeted epitopes with greater evolutionary conservation (mean entropy [±SD], 0.32 ± 0.1 bits; P = .003), and epitopes recognized by responders provided higher coverage (49%; P = .035). Heterologous vector regimens had higher numbers of total, EnvA, and EnvB epitopes than homologous vector regimens (P = .02, .044, and .045, respectively).

CONCLUSIONS:

These data demonstrate that vaccination with heterologous insert prime boosting increased T-cell responses to shared epitopes, while heterologous vector prime boosting increased the number of T-cell epitopes recognized.

CLINICAL TRIALS REGISTRATION:

NCT01095224.

KEYWORDS:

HIV-1; adenovirus; clinical trial; epitope mapping; immunogenicity; prime-boost; vaccines

PMID:
26475930
PMCID:
PMC4721914
DOI:
10.1093/infdis/jiv496
[Indexed for MEDLINE]
Free PMC Article

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