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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.
SUBMITTER: Goepfert PA
PROVIDER: S-EPMC4072895 | biostudies-literature | 2014 Jul
REPOSITORIES: biostudies-literature
Goepfert Paul A PA Elizaga Marnie L ML Seaton Kelly K Tomaras Georgia D GD Montefiori David C DC Sato Alicia A Hural John J DeRosa Stephen C SC Kalams Spyros A SA McElrath M Juliana MJ Keefer Michael C MC Baden Lindsey R LR Lama Javier R JR Sanchez Jorge J Mulligan Mark J MJ Buchbinder Susan P SP Hammer Scott M SM Koblin Beryl A BA Pensiero Michael M Butler Chris C Moss Bernard B Robinson Harriet L HL
The Journal of infectious diseases 20140107 1
<h4>Background</h4>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.<h4>Methods</h4>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 regime ...[more]