title: Vaccine-induced early control of hepatitis C virus infection in chimpanzees fails to impact on hepatic PD-1 and chronicity.
abstract: Broad T cell and B cell responses to multiple HCV antigens are observed early in individuals who control or clear HCV infection. The prevailing hypothesis has been that similar immune responses induced by prophylactic immunization would reduce acute virus replication and protect exposed individuals from chronic infection. Here, we demonstrate that immunization of naïve chimpanzees with a multicomponent HCV vaccine induced robust HCV-specific immune responses, and that all vaccinees exposed to heterologous chimpanzee-adapted HCV 1b J4 significantly reduced viral RNA in serum by 84%, and in liver by 99% as compared to controls (P=0.024 and 0.028, respectively). However, despite control of HCV in plasma and liver in the acute period, in the chronic phase, 3 of 4 vaccinated animals developed persistent infection. Analysis of expression levels of proinflammatory cytokines in serial hepatic biopsies failed to reveal an association with vaccine outcome. However, expression of IDO, CTLA-4 [corrected] and PD-1 levels in liver correlated with clearance or chronicity.
  
  
  CONCLUSIONS
  Despite early control of virus load, a virus-associated tolerogenic-like state can develop in certain individuals independent of vaccination history.
authors.affiliation: Department of Virology, Biomedical Primate Research Center, GH Rijswijk, The Netherlands.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Rollier
authors.forename: Glaucia
authors.initials: G
authors.lastname: Paranhos-Baccala
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Verschoor
authors.forename: Babs E
authors.initials: BE
authors.lastname: Verstrepen
authors.forename: Joost A R
authors.initials: JA
authors.lastname: Drexhage
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fagrouch
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Berland
authors.forename: Florence
authors.initials: F
authors.lastname: Komurian-Pradel
authors.forename: Blandine
authors.initials: B
authors.lastname: Duverger
authors.forename: Nourredine
authors.initials: N
authors.lastname: Himoudi
authors.forename: Caroline
authors.initials: C
authors.lastname: Staib
authors.forename: Marcus
authors.initials: M
authors.lastname: Meyr
authors.forename: Mike
authors.initials: M
authors.lastname: Whelan
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Whelan
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Adams
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Adams
authors.forename: Esther
authors.initials: E
authors.lastname: Larrea
authors.forename: José I
authors.initials: JI
authors.lastname: Riezu
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lasarte
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lasarte
authors.forename: Birke
authors.initials: B
authors.lastname: Bartosch
authors.forename: Francois-L
authors.initials: FL
authors.lastname: Cosset
authors.forename: Willy J M
authors.initials: WJ
authors.lastname: Spaan
authors.forename: Helmut M
authors.initials: HM
authors.lastname: Diepolder
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Pape
authors.forename: Gerd
authors.initials: G
authors.lastname: Sutter
authors.forename: Genevieve
authors.initials: G
authors.lastname: Inchauspe
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000956:Antigens, Viral / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002908:Chronic Disease / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology* / Q000517:prevention & control; D002679:Pan troglodytes; D061026:Programmed Cell Death 1 Receptor; D014761:Viral Hepatitis Vaccines / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D015703:Antigens, CD; D000956:Antigens, Viral; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D004279:DNA, Viral; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D014761:Viral Hepatitis Vaccines