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

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.

• Authors: Paul A Goepfert, Marnie L Elizaga, Kelly Seaton, Georgia D Tomaras, David C Montefiori, Alicia Sato, John Hural, Stephen C DeRosa, Spyros A Kalams, M Juliana McElrath, Michael C Keefer, Lindsey R Baden, Javier R Lama, Jorge Sanchez, Mark J Mulligan, Susan P Buchbinder, Scott M Hammer, Beryl A Koblin, Michael Pensiero, Chris Butler, Bernard Moss, Harriet L Robinson, HVTN 205 Study Group, National Institutes of Allergy and Infectious Diseases HIV Vaccines Trials Network
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 210 Issue 1 Pg. 99-110 (Jul 01 2014) ISSN: 1537-6613 [Electronic] United States
• PMID: 24403557 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © 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: [email protected].

Chemical References

• AIDS Vaccines
• Drug Carriers
• HIV Antibodies
• Placebos
• Vaccines, Synthetic
• Vaccines, Virus-Like Particle
• env Gene Products, Human Immunodeficiency Virus

Topics

• AIDS Vaccines (administration & dosage, genetics, immunology)
• Adolescent
• Adult
• Drug Carriers
• Female
• HIV Antibodies (blood)
• HIV-1 (genetics, immunology)
• Humans
• Male
• Middle Aged
• Placebos (administration & dosage)
• T-Lymphocytes (immunology)
• Time Factors
• Vaccines, Synthetic (administration & dosage, genetics, immunology)
• Vaccines, Virus-Like Particle (administration & dosage, genetics, immunology)
• Vaccinia virus (genetics)
• Young Adult
• env Gene Products, Human Immunodeficiency Virus (genetics, immunology)