PLoS ONE (Jan 2017)

Immunogenicity of a novel Clade B HIV-1 vaccine combination: Results of phase 1 randomized placebo controlled trial of an HIV-1 GM-CSF-expressing DNA prime with a modified vaccinia Ankara vaccine boost in healthy HIV-1 uninfected adults.

  • Susan P Buchbinder,
  • Nicole A Grunenberg,
  • Brittany J Sanchez,
  • Kelly E Seaton,
  • Guido Ferrari,
  • M Anthony Moody,
  • Nicole Frahm,
  • David C Montefiori,
  • Christine M Hay,
  • Paul A Goepfert,
  • Lindsey R Baden,
  • Harriet L Robinson,
  • Xuesong Yu,
  • Peter B Gilbert,
  • M Juliana McElrath,
  • Yunda Huang,
  • Georgia D Tomaras,
  • HIV Vaccine Trials Network (HVTN) 094 Study Group

DOI
https://doi.org/10.1371/journal.pone.0179597
Journal volume & issue
Vol. 12, no. 7
p. e0179597

Abstract

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BACKGROUNDA phase 1 trial of a clade B HIV vaccine in HIV-uninfected adults evaluated the safety and immunogenicity of a DNA prime co-expressing GM-CSF (Dg) followed by different numbers and intervals of modified vaccinia Ankara Boosts (M). Both vaccines produce virus-like particles presenting membrane-bound Env.METHODSFour US sites randomized 48 participants to receiving 1/10th the DNA dose as DgDgMMM given at 0, 2, 4, 6 and 8 months, or full dose DgDgM_M or DgDgMM_M regimens, given at 0, 2, 4, and 8 months, and 0, 2, 4, 6, and 10 months, respectively. Peak immunogenicity was measured 2 weeks post-last vaccination.RESULTSAll regimens were well tolerated and safe. Full dose DgDgM_M and DgDgMM_M regimens generated Env-specific IgG to HIV-1 Env in >90%, IgG3 in >80%, and IgA in CONCLUSIONThis DNA/MVA prime-boost regimen induced durable, functional humoral responses that included ADCC, high antibody avidity, and Env IgG1 and IgG3 binding responses to the immunodominant region of gp41. The third, spaced MVA boost improved the overall quality of the antibody response. These products without co-expressed GM-CSF but combined with protein boosts will be considered for efficacy evaluation.TRIAL REGISTRATIONClinicalTrials.gov NCT01571960.