title: Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.
abstract: 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.
  
  
  BACKGROUND
  Controlled-Trials ISRCTN90053831 The Pan African Clinical Trials Registry ATMR2009040001075080 (currently PACTR2009040001075080).
authors: Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors: Agricola
authors: A
authors: Joachim
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Public Health Agency of Sweden, Solna, Sweden; Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
authors: Charlotta
authors: C
authors: Nilsson
authors: Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
authors: Said
authors: S
authors: Aboud
authors: Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
authors: Muhammad
authors: M
authors: Bakari
authors: Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
authors: Eligius F
authors: EF
authors: Lyamuya
authors: The Military HIV Research Program, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America.
authors: Merlin L
authors: ML
authors: Robb
authors: The Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Mary A
authors: MA
authors: Marovich
authors: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Patricia
authors: P
authors: Earl
authors: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Bernard
authors: B
authors: Moss
authors: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors: Christina
authors: C
authors: Ochsenbauer
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors: Britta
authors: B
authors: Wahren
authors: Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
authors: Fred
authors: F
authors: Mhalu
authors: Venhälsan, Karolinska Institutet at Södersjukhuset, Stockholm, Sweden.
authors: Eric
authors: E
authors: Sandström
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Public Health Agency of Sweden, Solna, Sweden.
authors: Gunnel
authors: G
authors: Biberfeld
authors: Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America.
authors: Guido
authors: G
authors: Ferrari
authors: The Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Victoria R
authors: VR
authors: Polonis
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D000937:Antigen-Antibody Reactions; D004279:DNA, Viral / Q000276:immunology*; D004311:Double-Blind Method; D015752:Genes, env; D015750:Genes, gag; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000097:blood; D015488:HIV Antigens / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007694:Killer Cells, Natural / Q000276:immunology; D013636:Tanzania; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D004279:DNA, Viral; D015483:HIV Antibodies; D015488:HIV Antigens; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic