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- Title
A heterologous prime/boost vaccination strategy enhances the immunogenicity of therapeutic vaccines for hepatitis C virus.
- Authors
Fournillier, Anne; Frelin, Lars; Jacquier, Emilie; Ahlén, Gustaf; Brass, Anette; Gerossier, Estelle; Holmström, Fredrik; Broderick, Kate E; Sardesai, Niranjan Y; Bonnefoy, Jean-Yves; Inchauspé, Geneviève; Sällberg, Matti
- Abstract
<bold>Background: </bold>We explored the concept of heterologous prime/boost vaccination using 2 therapeutic vaccines currently in clinical development aimed at treating chronically infected hepatitis C virus (HCV) patients: prime with a DNA-based vaccine expressing HCV genotype 1a NS3/4A proteins (ChronVac-C) and boost with a modified vaccinia virus Ankara vaccine expressing genotype 1b NS3/4/5B proteins (MVATG16643).<bold>Methods: </bold>Two ChronVac-C immunizations 4 weeks apart were delivered intramuscularly in combination with in vivo electroporation and subsequently 5 or 12 weeks later boosted by 3 weekly subcutaneous injections of MVATG16643. Two mouse strains were used, and we evaluated quality, magnitude, and functionality of the T cells induced.<bold>Results: </bold>DNA prime/MVA boost regimen induced significantly higher levels of interferon γ (IFN-γ) or interleukin 2 (IL-2) ELISpot responses compared with each vaccine alone, independent of the time of analysis and the time interval between vaccinations. Both CD8⁺ and CD4⁺ T-cell responses as well as the spectrum of epitopes recognized was improved. A significant increase in polyfunctional IFN-γ/tumor necrosis factor α (TNF-α)/CD107a⁺ CD8⁺ T cells was detected following ChronVac-C/MVATG16643 vaccination (from 3% to 25%), and prime/boost was the only regimen that activated quadrifunctional T cells (IFN-γ/TNF-α/CD107a/IL-2). In vivo functional protective capacity of DNA prime/MVA boost was demonstrated in a Listeria-NS3-1a challenge model.<bold>Conclusions: </bold>We provide a proof-of-concept that immunogenicity of 2 HCV therapeutic vaccines can be improved using their combination, which merits further clinical development.
- Publication
Journal of Infectious Diseases, 2013, Vol 208, Issue 6, p1008
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jit267