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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. 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
dc.coverage.spatial United States 2015-10-09T15:39:57Z 2015
dc.identifier PONE-D-14-36854
dc.description.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).
dc.language eng
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0118486
dc.subject AIDS Vaccines
dc.subject Adult
dc.subject Antibodies, Neutralizing
dc.subject Antibody-Dependent Cell Cytotoxicity
dc.subject Antigen-Antibody Reactions
dc.subject DNA, Viral
dc.subject Double-Blind Method
dc.subject Genes, env
dc.subject Genes, gag
dc.subject HIV Antibodies
dc.subject HIV Antigens
dc.subject HIV-1
dc.subject Humans
dc.subject Immunization, Secondary
dc.subject Killer Cells, Natural
dc.subject Tanzania
dc.subject Vaccination
dc.subject Vaccines, DNA
dc.subject Vaccines, Synthetic
dc.subject Vaccinia virus
dc.title Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.
dc.type Journal article Ferrari, Guido|0108355
pubs.begin-page e0118486
pubs.issue 4
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Global Health Institute
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Sciences
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published online
pubs.volume 10
dc.identifier.eissn 1932-6203
duke.contributor.orcid Ferrari, Guido|0000-0001-7747-3349

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