title: Three-Year Durability of Immune Responses Induced by HIV-DNA and HIV-Modified Vaccinia Virus Ankara and Effect of a Late HIV-Modified Vaccinia Virus Ankara Boost in Tanzanian Volunteers.
abstract: We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization 3 years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100). The majority of vaccinees had detectable antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, 70% against CRF01_AE virus-infected cells (median titer 239) and 84% against CRF01_AE gp120-coated cells (median titer 499). A high proportion (74%) of vaccinees had IFN-γ ELISpot responses, 63% to Gag and 42% to Env, 3 years after the second HIV-MVA boost. After the third HIV-MVA, there was an increase in Env-binding antibodies and ADCC-mediating antibodies relative to the response seen at the time of the third HIV-MVA vaccination, p < .0001 and p < .05, respectively. The frequency of IFN-γ ELISpot responses increased to 95% against Gag or Env and 90% to both Gag and Env, p = .064 and p = .002, respectively. In conclusion, the HIV-DNA prime/HIV-MVA boost regimen elicited potent antibody and cellular immune responses with remarkable durability, and a third HIV-MVA immunization significantly boosted both antibody and cellular immune responses relative to the levels detected at the time of the third HIV-MVA, but not to higher levels than after the second HIV-MVA.
authors.affiliation: 1 Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS) , Dar es Salaam, Tanzania .|2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Agricola
authors.initials: A
authors.lastname: Joachim
authors.affiliation: 3 Department of Internal Medicine, Muhimbili University of Health and Allied Sciences (MUHAS) , Dar es Salaam, Tanzania .
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Munseri
authors.affiliation: 2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm, Sweden .|4 Department of Laboratory Medicine, Karolinska Institutet , Huddinge, Sweden .|5 Public Health Agency of Sweden , Solna, Sweden .
authors.forename: Charlotta
authors.initials: C
authors.lastname: Nilsson
authors.affiliation: 3 Department of Internal Medicine, Muhimbili University of Health and Allied Sciences (MUHAS) , Dar es Salaam, Tanzania .
authors.forename: Muhammad
authors.initials: M
authors.lastname: Bakari
authors.affiliation: 1 Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS) , Dar es Salaam, Tanzania .
authors.forename: Said
authors.initials: S
authors.lastname: Aboud
authors.affiliation: 1 Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS) , Dar es Salaam, Tanzania .
authors.forename: Eligius F
authors.initials: EF
authors.lastname: Lyamuya
authors.affiliation: 5 Public Health Agency of Sweden , Solna, Sweden .
authors.forename: Teghesti
authors.initials: T
authors.lastname: Tecleab
authors.affiliation: 2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm, Sweden .|6 Faculty of Medicine, Vilnius University , Vilnius, Lithuania .
authors.forename: Valentina
authors.initials: V
authors.lastname: Liakina
authors.affiliation: 7 Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute , Milan, Italy .
authors.forename: Gabriella
authors.initials: G
authors.lastname: Scarlatti
authors.affiliation: 8 The Military HIV Research Program, The Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda, Maryland.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: 9 National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH) , Bethesda, Maryland.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.affiliation: 9 National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH) , Bethesda, Maryland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.affiliation: 2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Britta
authors.initials: B
authors.lastname: Wahren
authors.affiliation: 1 Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS) , Dar es Salaam, Tanzania .
authors.forename: Fred
authors.initials: F
authors.lastname: Mhalu
authors.affiliation: 10 Department of Surgery and Molecular Genetics and Microbiology, Duke University Medical Center , Durham, North Carolina.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: 11 Venhälsan, Karolinska Institutet , Södersjukhuset, Stockholm, Sweden .
authors.forename: Eric
authors.initials: E
authors.lastname: Sandstrom
authors.affiliation: 2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm, Sweden .|5 Public Health Agency of Sweden , Solna, Sweden .
authors.forename: Gunnel
authors.initials: G
authors.lastname: Biberfeld
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D056704:Adaptive Immunity; D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity; D004337:Drug Carriers; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000276:immunology*; D064368:Healthy Volunteers; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013636:Tanzania; D013997:Time Factors; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D015483:HIV Antibodies; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma
keywords: DNA; HIV; MVA; immune response; vaccine