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Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.

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Date
2015
Authors
Joachim, Agricola
Nilsson, Charlotta
Aboud, Said
Bakari, Muhammad
Lyamuya, Eligius F
Robb, Merlin L
Marovich, Mary A
Earl, Patricia
Moss, Bernard
Ochsenbauer, Christina
Wahren, Britta
Mhalu, Fred
Sandström, Eric
Biberfeld, Gunnel
Ferrari, Guido
Polonis, Victoria R
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(16 total)
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Abstract
UNLABELLED: Vaccine-induced HIV antibodies were evaluated in serum samples collected from healthy Tanzanian volunteers participating in a phase I/II placebo-controlled double blind trial using multi-clade, multigene HIV-DNA priming and recombinant modified vaccinia Ankara (HIV-MVA) virus boosting (HIVIS03). The HIV-DNA vaccine contained plasmids expressing HIV-1 gp160 subtypes A, B, C, Rev B, Gag A, B and RTmut B, and the recombinant HIV-MVA boost expressed CRF01_AE HIV-1 Env subtype E and Gag-Pol subtype A. While no neutralizing antibodies were detected using pseudoviruses in the TZM-bl cell assay, this prime-boost vaccination induced neutralizing antibodies in 83% of HIVIS03 vaccinees when a peripheral blood mononuclear cell (PBMC) assay using luciferase reporter-infectious molecular clones (LucR-IMC) was employed. The serum neutralizing activity was significantly (but not completely) reduced upon depletion of natural killer (NK) cells from PBMC (p=0.006), indicating a role for antibody-mediated Fcγ-receptor function. High levels of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies against CRF01_AE and/or subtype B were subsequently demonstrated in 97% of the sera of vaccinees. The magnitude of ADCC-mediating antibodies against CM235 CRF01_AE IMC-infected cells correlated with neutralizing antibodies against CM235 in the IMC/PBMC assay. In conclusion, HIV-DNA priming, followed by two HIV-MVA boosts elicited potent ADCC responses in a high proportion of Tanzanian vaccinees. Our findings highlight the potential of HIV-DNA prime HIV-MVA boost vaccines for induction of functional antibody responses and suggest this vaccine regimen and ADCC studies as potentially important new avenues in HIV vaccine development. TRIAL REGISTRATION: Controlled-Trials ISRCTN90053831 The Pan African Clinical Trials Registry ATMR2009040001075080 (currently PACTR2009040001075080).
Type
Journal article
Subject
AIDS Vaccines
Adult
Antibodies, Neutralizing
Antibody-Dependent Cell Cytotoxicity
Antigen-Antibody Reactions
DNA, Viral
Double-Blind Method
Genes, env
Genes, gag
HIV Antibodies
HIV Antigens
HIV-1
Humans
Immunization, Secondary
Killer Cells, Natural
Tanzania
Vaccination
Vaccines, DNA
Vaccines, Synthetic
Vaccinia virus
Permalink
https://hdl.handle.net/10161/10731
Published Version (Please cite this version)
10.1371/journal.pone.0118486
Publication Info
Joachim, Agricola; Nilsson, Charlotta; Aboud, Said; Bakari, Muhammad; Lyamuya, Eligius F; Robb, Merlin L; ... Polonis, Victoria R (2015). Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults. PLoS One, 10(4). pp. e0118486. 10.1371/journal.pone.0118486. Retrieved from https://hdl.handle.net/10161/10731.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Ferrari

Guido Ferrari

Professor in Surgery
The activities of the Ferrari Laboratory are based on both independent basic research and immune monitoring studies. The research revolves around three main areas of interest: class I-mediated cytotoxic CD8+ T cell responses, antibody-dependent cellular cytotoxicity (ADCC), gene expression in NK and T cellular subsets upon infection with HIV-1. With continuous funding over the last 11 years from the NIH and Bill & Melinda Gates Foundation along with many other productive collaborations wi
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