Epitopes described in "A heterologous prime/boost vaccination strategy enhances the immunogenicity of therapeutic vaccines for hepatitis C virus."

Article Authors:Anne Fournillier; Lars Frelin; Emilie Jacquier; Gustaf Ahlén; Anette Brass; Estelle Gerossier; Fredrik Holmström; Kate E Broderick; Niranjan Y Sardesai; Jean-Yves Bonnefoy; Geneviève Inchauspé; Matti Sällberg
Article Title:A heterologous prime/boost vaccination strategy enhances the immunogenicity of therapeutic vaccines for hepatitis C virus.
Reference Detail
Reference ID:1026728
Abstract:BACKGROUND: 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). METHODS: 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. RESULTS: DNA prime/MVA boost regimen induced significantly higher levels of interferon (IFN-) 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-/tumor necrosis factor (TNF-)/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-/TNF-/CD107a/IL-2). In vivo functional protective capacity of DNA prime/MVA boost was demonstrated in a Listeria-NS3-1a challenge model. CONCLUSIONS: We provide a proof-of-concept that immunogenicity of 2 HCV therapeutic vaccines can be improved using their combination, which merits further clinical development.
Affiliations:Département des Maladies Infectieuses, Transgene SA, Centre d'Infectiologie, Lyon, France.
Reference Type:Literature
PubMed ID:23776192
Journal:J Infect Dis
Journal Volume:208
Article Pages:1008-19
Journal ISSN:0022-1899
Article Chemical List:Interleukin-2;Tumor Necrosis Factor-alpha;Vaccines, DNA;Viral Hepatitis Vaccines;Interferon-gamma
Article MeSH List:Animals; Antibody Formation; CD4-Positive T-Lymphocytes(immunology); CD8-Positive T-Lymphocytes(immunology); Genotype; Hepacivirus; Hepatitis C(immunology; prevention & control); Immunization, Secondary; Interferon-gamma(blood); Interleukin-2(blood); Mice; Mice, Inbred C57BL; Mice, Transgenic; Tumor Necrosis Factor-alpha(blood); Vaccination(methods); Vaccines, DNA(immunology); Viral Hepatitis Vaccines(genetics; immunology)
Curation Last Updated:2015-07-30 20:48:37