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PLoS One. 2015 Apr 15;10(4):e0119629. doi: 10.1371/journal.pone.0119629. eCollection 2015.

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.

Author information

  • 1Department of Internal Medicine, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania; Venhalsan, Karolinska Institutet, Sodersjukhuset, Stockholm, Sweden.
  • 2National 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.
  • 3The 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.
  • 4Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
  • 5Department 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.
  • 6National 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.
  • 7Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
  • 8National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.
  • 9National Institute for Medical Research-Muhimbili Medical Research Centre, Dar es Salaam, Tanzania.
  • 10The Public Health Agency of Sweden, Solna, Sweden.
  • 11Walter Reed Army Institute of Research (WRAIR), Rockville, MD, United States of America and The Henry M. Jackson Foundation, Rockville, MD, United States of America.
  • 12Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD, United States of America.
  • 13Imperial College, London, United Kingdom.
  • 14Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom.
  • 15Bioject Medical Technologies, 7180 SW Sandburg St, Tigard, Oregon, United States of America.
  • 16Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden.
  • 17The Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden.
  • 18Venhalsan, Karolinska Institutet, Sodersjukhuset, Stockholm, Sweden.
  • 19Department of Internal Medicine, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.

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.

TRIAL REGISTRATION:

World Health Organization International Clinical Trials Registry Platform PACTR2010050002122368.

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