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Potent cellular and humoral immunity against HIV-1 elicited in mice by a DNA-prime/MVA-boost vaccine regimen intended for human use

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In an experimental vaccine model, mice were primed three times with plasmids encoding multiple subtypes (A, B and C) of gag, envelope (env) and reverse transcriptase (RT) and adjuvant rGM-CSF followed by modified vaccinica Ankara (MVA) with the recombinant form A_E, in theory providing protection against HIV subtypes A-E. The cellular responses, as measured by IFN-gamma secretion gave up to 2000 gag-specific SFC/million PBMC. The humoral and cellular responses were further increased by the MVA-boosts with env and gag specific ELISpot responses above 3500 secreting/106 cells. Intracellular cytokine staining showed remarkably high numbers (~15%) of gag and env specific CD8+ T cells. This paved the way for our clinical trial with the multigene/multisubtype DNA plasmids boosted with the MVA construct. Conclusions: This preclinical study clearly shows the potential of combining these particular DNA and MVAs in a prime/boost regimen and that it is possible to induce a strong and broad humoral and cellular response directed against several parts of HIV as well as to several subtypes of the virus.

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Correspondence to Britta Wahren.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Clinical Trial
  • Infectious Disease
  • Cancer Research
  • Reverse Transcriptase
  • Cellular Response