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

Authors :
Goepfert, Paul A.
Elizaga, Marnie L.
Seaton, Kelly
Tomaras, Georgia D.
Montefiori, David C.
Sato, Alicia
Hural, John
DeRosa, Stephen C.
Kalams, Spyros A.
McElrath, M. Juliana
Keefer, Michael C.
Baden, Lindsey R.
Lama, Javier R.
Sanchez, Jorge
Mulligan, Mark J.
Buchbinder, Susan P.
Hammer, Scott M.
Koblin, Beryl A.
Pensiero, Michael
Butler, Chris
Source :
Journal of Infectious Diseases. 2014 Jul 1, Vol. 210 Issue 1, p99-110. 12p. 7 Graphs.
Publication Year :
2014

Abstract

<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>DDMM and MMM vaccinations with virus-like particle-expressing immunogens elicited durable antibody and T-cell responses. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00221899
Volume :
210
Issue :
1
Database :
Academic Search Index
Journal :
Journal of Infectious Diseases
Publication Type :
Academic Journal
Accession number :
107857449
Full Text :
https://doi.org/10.1093/infdis/jiu003