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 and Muhammad Bakari

PLOS ONE, 2015, vol. 10, issue 4, 1-21

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

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0119629

DOI: 10.1371/journal.pone.0119629

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