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J Infect Dis. 2014 Jul 1;210(1):99-110. doi: 10.1093/infdis/jiu003. Epub 2014 Jan 7.

Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles.

Author information

1
Department of Medicine, University of Alabama at Birmingham.
2
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
3
Laboratory for AIDS Vaccine Research and Development, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
4
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center University of Washington, Seattle, Washington.
5
Vanderbilt University School of Medicine, Nashville, Tennessee.
6
University of Rochester School of Medicine and Dentistry, Rochester.
7
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
8
Asociacion Civil IMPACTA Salud y Educacion, Lima, Peru.
9
Division of Infectious Diseases, Emory University, Atlanta.
10
Bridge HIV, San Francisco Department of Public Health, California.
11
Columbia University.
12
New York Blood Center, New York, New York.
13
Division of AIDS.
14
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
15
GeoVax Inc., Smyrna, Georgia.

Abstract

BACKGROUND:

Clade B DNA and recombinant modified vaccinia Ankara (MVA) vaccines producing virus-like particles displaying trimeric membrane-bound envelope glycoprotein (Env) were tested in a phase 2a trial in human immunodeficiency virus (HIV)-uninfected adults for safety, immunogenicity, and 6-month durability of immune responses.

METHODS:

A total of 299 individuals received 2 doses of JS7 DNA vaccine and 2 doses of MVA/HIV62B at 0, 2, 4, and 6 months, respectively (the DDMM regimen); 3 doses of MVA/HIV62B at 0, 2, and 6 months (the MMM regimen); or placebo injections.

RESULTS:

At peak response, 93.2% of the DDMM group and 98.4% of the MMM group had binding antibodies for Env. These binding antibodies were more frequent and of higher magnitude for the transmembrane subunit (gp41) than the receptor-binding subunit (gp120) of Env. For both regimens, response rates were higher for CD4(+) T cells (66.4% in the DDMM group and 43.1% in the MMM group) than for CD8(+) T cells (21.8% in the DDMM group and 14.9% in the MMM group). Responding CD4(+) and CD8(+) T cells were biased toward Gag, and >70% produced 2 or 3 of the 4 cytokines evaluated (ie, interferon γ, interleukin 2, tumor necrosis factor α, and granzyme B). Six months after vaccination, the magnitudes of antibodies and T-cell responses had decreased by <3-fold.

CONCLUSIONS:

DDMM and MMM vaccinations with virus-like particle-expressing immunogens elicited durable antibody and T-cell responses.

KEYWORDS:

DNA; HIV/AIDS; T cells; antibodies; clinical trial; recombinant MVA; vaccines

PMID:
24403557
PMCID:
PMC4072895
DOI:
10.1093/infdis/jiu003
[Indexed for MEDLINE]
Free PMC Article

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