title: T- and B-cell responses to multivalent prime-boost DNA and viral vectored vaccine combinations against hepatitis C virus in non-human primates.
abstract: Immune responses against multiple epitopes are required for the prevention of hepatitis C virus (HCV) infection, and the progression to phase I trials of candidates may be guided by comparative immunogenicity studies in non-human primates. Four vectors, DNA, SFV, human serotype 5 adenovirus (HuAd5) and Modified Vaccinia Ankara (MVA) poxvirus, all expressing hepatitis C virus Core, E1, E2 and NS3, were combined in three prime-boost regimen, and their ability to elicit immune responses against HCV antigens in rhesus macaques was explored and compared. All combinations induced specific T-cell immune responses, including high IFN-γ production. The group immunized with the SFV+MVA regimen elicited higher E2-specific responses as compared with the two other modalities, while animals receiving HuAd5 injections elicited lower IL-4 responses as compared with those receiving MVA. The IFN-γ responses to NS3 were remarkably similar between groups. Only the adenovirus induced envelope-specific antibody responses, but these failed to show neutralizing activity. Therefore, the two novel regimens failed to induce superior responses as compared with already existing HCV vaccine candidates. Differences were found in response to envelope proteins, but the relevance of these remain uncertain given the surprisingly poor correlation with immunogenicity data in chimpanzees, underlining the difficulty to predict efficacy from immunology studies.
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.|Department of Paediatrics, Oxford Vaccine Group, CCVTM Churchill Hospital, University of Oxford, Oxford, UK.
authors.forename: C S
authors.initials: CS
authors.lastname: Rollier
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: Verschoor
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: B E
authors.initials: BE
authors.lastname: Verstrepen
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: J A R
authors.initials: JA
authors.lastname: Drexhage
authors.affiliation: UMR2714, CNRS-BioMérieux, IFR 128 Biosciences Gerland, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Paranhos-Baccala
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Liljeström
authors.affiliation: GSF Institut für Molekular Virology, Munich, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Sutter
authors.affiliation: Immunology and Immunotherapy Program, Center for Applied Medical Research (CIMA), University of Navarra, IdiSNA, Pamplona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Arribillaga
authors.affiliation: Immunology and Immunotherapy Program, Center for Applied Medical Research (CIMA), University of Navarra, IdiSNA, Pamplona, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lasarte
authors.affiliation: CIRI-International Center for Infectiology Research, Université de Lyon; Inserm, U1111; Ecole Normale Supérieure de Lyon; Université Lyon 1, Centre International de Recherche en Infectiologie; CNRS, UMR5308; LabEx Ecofect, Université de Lyon, Lyon, France.
authors.forename: B
authors.initials: B
authors.lastname: Bartosch
authors.affiliation: CIRI-International Center for Infectiology Research, Université de Lyon; Inserm, U1111; Ecole Normale Supérieure de Lyon; Université Lyon 1, Centre International de Recherche en Infectiologie; CNRS, UMR5308; LabEx Ecofect, Université de Lyon, Lyon, France.
authors.forename: F-L
authors.initials: FL
authors.lastname: Cosset
authors.affiliation: UMR2714, CNRS-BioMérieux, IFR 128 Biosciences Gerland, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Inchauspe
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: J L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D000939:Epitopes / Q000235:genetics* / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics; D016174:Hepacivirus / Q000276:immunology*; D000071497:Immunogenicity, Vaccine; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008253:Macaca mulatta; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000939:Epitopes; D014761:Viral Hepatitis Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma