Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.
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 articleSubject
AIDS VaccinesAdult
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
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https://hdl.handle.net/10161/10731Published Version (Please cite this version)
10.1371/journal.pone.0118486Publication 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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Show full item recordScholars@Duke
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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