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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

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

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

KEYWORDS:

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

PMID:
24403557
[PubMed - indexed for MEDLINE]
PMCID:
PMC4072895
[Available on 2015-07-01]

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