PLoS ONE (Jan 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.

  • Patricia J Munseri,
  • Arne Kroidl,
  • Charlotta Nilsson,
  • Agricola Joachim,
  • Christof Geldmacher,
  • Philipp Mann,
  • Candida Moshiro,
  • Said Aboud,
  • Eligius Lyamuya,
  • Leonard Maboko,
  • Marco Missanga,
  • Bahati Kaluwa,
  • Sayoki Mfinanga,
  • Lilly Podola,
  • Asli Bauer,
  • Karina Godoy-Ramirez,
  • Mary Marovich,
  • Bernard Moss,
  • Michael Hoelscher,
  • Frances Gotch,
  • Wolfgang Stöhr,
  • Richard Stout,
  • Sheena McCormack,
  • Britta Wahren,
  • Fred Mhalu,
  • Merlin L Robb,
  • Gunnel Biberfeld,
  • Eric Sandström,
  • Muhammad Bakari

Journal volume & issue
Vol. 10, no. 4
p. e0119629


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BackgroundIntradermal 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.MethodsIn 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.Results129 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.ConclusionsA 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 registrationWorld Health Organization International Clinical Trials Registry Platform PACTR2010050002122368.