title: Priming with a simplified intradermal HIV-1 DNA vaccine regimen followed by boosting with recombinant HIV-1 MVA vaccine is safe and immunogenic: a phase IIa randomized clinical trial.
abstract: BACKGROUND
  Intradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools.
  
  
  METHODS
  In this phase IIa, randomized trial, priming was performed using 5 injections of HIV-DNA, 1000 μg total dose, (3 Env and 2 Gag encoding plasmids) compared to two "simplified" regimens of 2 injections of HIV-DNA, 600 μg total dose, of Env- and Gag-encoding plasmid pools with each pool either administered separately or combined. HIV-DNA immunizations were given intradermally at weeks 0, 4, and 12. Boosting was performed intramuscularly with 108 pfu HIV-MVA at weeks 30 and 46.
  
  
  RESULTS
  129 healthy Tanzanian participants were enrolled. There were no differences in adverse events between the groups. The proportion of IFN-γ ELISpot responders to Gag and/or Env peptides after the second HIV-MVA boost did not differ significantly between the groups primed with 2 injections of combined HIV-DNA pools, 2 injections with separated pools, and 5 injections with separated pools (90%, 97% and 97%). There were no significant differences in the magnitude of Gag and/or Env IFN-γ ELISpot responses, in CD4+ and CD8+ T cell responses measured as IFN-γ/IL-2 production by intracellular cytokine staining (ICS) or in response rates and median titers for binding antibodies to Env gp160 between study groups.
  
  
  CONCLUSIONS
  A simplified intradermal vaccination regimen with 2 injections of a total of 600 μg with combined HIV-DNA plasmids primed cellular responses as efficiently as the standard regimen of 5 injections of a total of 1000 μg with separated plasmid pools after boosting twice with HIV-MVA.
  
  
  BACKGROUND
  World Health Organization International Clinical Trials Registry Platform PACTR2010050002122368.
authors: Department of Internal Medicine, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania; Venhalsan, Karolinska Institutet, Sodersjukhuset, Stockholm, Sweden.
authors: Patricia J
authors: PJ
authors: Munseri
authors: National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania; Department of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich, Munich, Germany; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.
authors: Arne
authors: A
authors: Kroidl
authors: The Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, 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 (MUHAS), Dar es Salaam, Tanzania.
authors: Agricola
authors: A
authors: Joachim
authors: Department of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich, Munich, Germany; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.
authors: Christof
authors: C
authors: Geldmacher
authors: National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania; Department of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich, Munich, Germany.
authors: Philipp
authors: P
authors: Mann
authors: Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
authors: Candida
authors: C
authors: Moshiro
authors: Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
authors: Said
authors: S
authors: Aboud
authors: Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
authors: Eligius
authors: E
authors: Lyamuya
authors: National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.
authors: Leonard
authors: L
authors: Maboko
authors: National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.
authors: Marco
authors: M
authors: Missanga
authors: National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.
authors: Bahati
authors: B
authors: Kaluwa
authors: National Institute for Medical Research-Muhimbili Medical Research Centre, Dar es Salaam, Tanzania.
authors: Sayoki
authors: S
authors: Mfinanga
authors: National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania; Department of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich, Munich, Germany.
authors: Lilly
authors: L
authors: Podola
authors: National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania; Department of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich, Munich, Germany.
authors: Asli
authors: A
authors: Bauer
authors: The Public Health Agency of Sweden, Solna, Sweden.
authors: Karina
authors: K
authors: Godoy-Ramirez
authors: Walter Reed Army Institute of Research (WRAIR), Rockville, MD, United States of America and The Henry M. Jackson Foundation, Rockville, MD, United States of America.
authors: Mary
authors: M
authors: Marovich
authors: Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD, United States of America.
authors: Bernard
authors: B
authors: Moss
authors: National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania; Department of Infectious Diseases and Tropical Medicine, Klinikum of the University of Munich, Munich, Germany; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.
authors: Michael
authors: M
authors: Hoelscher
authors: Imperial College, London, United Kingdom.
authors: Frances
authors: F
authors: Gotch
authors: Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom.
authors: Wolfgang
authors: W
authors: Stöhr
authors: Bioject Medical Technologies, 7180 SW Sandburg St, Tigard, Oregon, United States of America.
authors: Richard
authors: R
authors: Stout
authors: Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom.
authors: Sheena
authors: S
authors: McCormack
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 (MUHAS), Dar es Salaam, Tanzania.
authors: Fred
authors: F
authors: Mhalu
authors: Walter Reed Army Institute of Research (WRAIR), Rockville, MD, United States of America and The Henry M. Jackson Foundation, Rockville, MD, United States of America.
authors: Merlin L
authors: ML
authors: Robb
authors: The Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden.
authors: Gunnel
authors: G
authors: Biberfeld
authors: Venhalsan, Karolinska Institutet, Sodersjukhuset, Stockholm, Sweden.
authors: Eric
authors: E
authors: Sandström
authors: Department of Internal Medicine, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
authors: Muhammad
authors: M
authors: Bakari
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage*; D000328:Adult; D004279:DNA, Viral / Q000008:administration & dosage; D064420:Drug-Related Side Effects and Adverse Reactions / Q000276:immunology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects / Q000276:immunology; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology; D013636:Tanzania; D019444:Vaccines, DNA / Q000008:administration & dosage*; D014765:Viral Vaccines / Q000008:administration & dosage*
chemical_list: D016915:AIDS Vaccines; D004279:DNA, Viral; C560489:MVA vaccine; D019444:Vaccines, DNA; D014765:Viral Vaccines