Journal Article

Potent Functional Antibody Responses Elicited by HIV-I DNA Priming and Boosting with Heterologous HIV-1 Recombinant MVA in Healthy Tanzanian Adults

Sandström, Eric, Polonis, Victoria R., Joachim, Agricola, Lyamuya, Eligius F., Wahren, Britta, Ferrari, Guido, Bakari, Muhammad, Marovich, Mary A., Aboud, Said, Robb, Merlin L., Nilsson, Charlotta, Biberfeld, Gunnel, Mhalu, Fred, Ochsenbauer, Christina, Earl, Patricia, Moss, Bernard

2015

Overview

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. Controlled-Trials ISRCTN90053831 The Pan African Clinical Trials Registry ATMR2009040001075080 (currently PACTR2009040001075080).

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Adults / AIDS vaccines / AIDS Vaccines - immunology / Antibodies / Antibodies, Neutralizing - biosynthesis / Antibodies, Neutralizing - immunology / Antibody-Dependent Cell Cytotoxicity / Antigen-Antibody Reactions / Assaying / Clinical trials / Cytotoxicity / Deoxyribonucleic acid / Development and progression / DNA / DNA vaccines / DNA, Viral - immunology / Double-Blind Method / Gag protein / Genes, env / Genes, gag / Glycoprotein gp160 / HIV / HIV antibodies / HIV Antibodies - biosynthesis / HIV Antibodies - blood / HIV Antigens - immunology / HIV-1 - genetics / HIV-1 - immunology / Human immunodeficiency virus / Humans / Immunization, Secondary / Killer Cells, Natural - immunology / Medical research / Natural killer cells / Neutralizing / Peripheral blood mononuclear cells / Plasmids / Priming / Tanzania / Toxicity / Vaccination / Vaccine development / Vaccines / Vaccines, DNA - immunology / Vaccines, Synthetic - immunology / Vaccinia virus - immunology / Viruses