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

Goepfert PA, Elizaga ML, Seaton K, Tomaras GD, Montefiori DC, Sato A, Hural J, DeRosa SC, Kalams SA, McElrath MJ, Keefer MC, Baden LR, Lama JR, Sanchez J, Mulligan MJ, Buchbinder SP, Hammer SM, Koblin BA, Pensiero M, Butler C, Moss B, Robinson HL, HVTN 205 Study Group, National Institutes of Allergy and Infectious Diseases HIV Vaccines Trials Network
J Infect Dis. 2014 210 (1): 99-110

PMID: 24403557 · PMCID: PMC4072895 · DOI:10.1093/infdis/jiu003

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.

MeSH Terms (18)

Adolescent Adult AIDS Vaccines Drug Carriers env Gene Products, Human Immunodeficiency Virus Female HIV-1 HIV Antibodies Humans Male Middle Aged Placebos T-Lymphocytes Time Factors Vaccines, Synthetic Vaccines, Virus-Like Particle Vaccinia virus Young Adult

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