Potent Functional Antibody Responses Elicited by HIV-I DNA Priming and Boosting with Heterologous HIV-1 Recombinant MVA in Healthy Tanzanian Adults.
In: PLoS ONE, Jg. 10 (2015-04-01), Heft 4, S. 1-15
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Zugriff:
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 The Pan African Clinical Trials Registry [ABSTRACT FROM AUTHOR]
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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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Autor/in / Beteiligte Person: | 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. |
Zeitschrift: | PLoS ONE, Jg. 10 (2015-04-01), Heft 4, S. 1-15 |
Veröffentlichung: | 2015 |
Medientyp: | academicJournal |
ISSN: | 1932-6203 (print) |
DOI: | 10.1371/journal.pone.0118486 |
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