title: Modulation of vaccine-induced immune responses to hepatitis C virus in rhesus macaques by altering priming before adenovirus boosting.
abstract: BACKGROUND
  Preventive and therapeutic vaccine strategies aimed at controlling hepatitis C virus (HCV) infection should mimic the immune responses observed in patients who control or clear HCV, specifically T helper (Th) type 1 and CD8+ cell responses to multiple antigens, including nonstructural protein (NS) 3. Given the experience with human immunodeficiency virus, the best candidates for this are based on DNA prime, pox, or adenovirus boost regimens.
  
  
  METHODS
  In rhesus macaques, we compared NS3-expressing DNA prime and adenovirus boost strategy with 2 alternative priming approaches aimed at modifying Th1 and CD8+ responses: DNA adjuvanted with interleukin (IL)-2- and -12-encoding plasmids or Semliki Forest virus (SFV).
  
  
  RESULTS
  All prime-boost regimens elicited NS3-specific B and T cell responses in rhesus macaques, including CD8+ responses. SFV priming induced higher lymphoproliferation and longer Th1 memory responses. The use of IL-2- and IL-12-expressing vectors resulted in reduced Th2 and antibody responses, which led to increased Th1 skewing but not to an increase in the magnitude of the IFN- gamma and CD8+ responses.
  
  
  CONCLUSIONS
  All strategies induced Th1 cellular responses to HCV NS3, with fine modulations depending on the different priming approaches. When they are developed for more HCV antigens, these strategies could be beneficial in therapeutic vaccine approaches.
authors.affiliation: Department of Virology, Biomedical Primate Research Center, Rijswijk, The Netherlands. rollier@bprc.nl
authors.forename: Christine
authors.initials: C
authors.lastname: Rollier
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Verschoor
authors.forename: Glaucia
authors.initials: G
authors.lastname: Paranhos-Baccala
authors.forename: Joost A R
authors.initials: JA
authors.lastname: Drexhage
authors.forename: Babs E
authors.initials: BE
authors.lastname: Verstrepen
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Berland
authors.forename: Nourredine
authors.initials: N
authors.lastname: Himoudi
authors.forename: Christina
authors.initials: C
authors.lastname: Barnfield
authors.forename: Peter
authors.initials: P
authors.lastname: Liljestrom
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Lasarte
authors.forename: Juan
authors.initials: J
authors.lastname: Ruiz
authors.forename: Genevieve
authors.initials: G
authors.lastname: Inchauspe
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D005822:Genetic Vectors / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D007114:Immunization / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008253:Macaca mulatta; D010446:Peptide Fragments / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000914:Antibodies, Viral; D007371:Interferon-gamma; D007376:Interleukin-2; D015847:Interleukin-4; D010446:Peptide Fragments; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases