title: Safety and immunogenicity of HCV E1E2 vaccine adjuvanted with MF59 administered to healthy adults.
abstract: BACKGROUND
  Hepatitis C virus (HCV) causes chronic liver disease that often leads to cirrhosis and hepatocellular carcinoma. In animal studies, chimpanzees were protected against chronic infection following experimental challenge with either homologous or heterologous HCV genotype 1a strains which predominate in the USA and Canada. We describe the first in humans clinical trial of this prophylactic HCV vaccine.
  
  
  METHODS
  HCV E1E2 adjuvanted with MF59C.1 (an oil-in-water emulsion) was given at 3 different dosages on day 0 and weeks 4, 24 and 48 in a phase 1, placebo-controlled, dose escalation trial to healthy HCV-negative adults.
  
  
  RESULTS
  There was no significant difference in the proportion of subjects reporting adverse events across the groups. Following vaccination subjects developed antibodies detectable by ELISA, CD81 neutralization and VSV/HCV pseudotype neutralization. There were no significant differences between vaccine groups in the number of responders and geometric mean titers for each of the three assays. All subjects developed lymphocyte proliferation responses to E1E2 and an inverse response to increasing amounts of antigen was noted.
  
  
  CONCLUSIONS
  The vaccine was safe and generally well-tolerated at each of the 3 dosage levels and induced antibody and lymphoproliferative responses. A larger study to further evaluate safety and immunogenicity is warranted.
authors.affiliation: Saint Louis University School of Medicine, Division of Infectious Diseases and Immunology, St. Louis, MO 63104, USA. freyse@slu.edu
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.forename: Michael
authors.initials: M
authors.lastname: Houghton
authors.forename: Stephen
authors.initials: S
authors.lastname: Coates
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.forename: David
authors.initials: D
authors.lastname: Chien
authors.forename: Domenico
authors.initials: D
authors.lastname: Rosa
authors.forename: Piero
authors.initials: P
authors.lastname: Pileri
authors.forename: Ranjit
authors.initials: R
authors.lastname: Ray
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: Paola
authors.initials: P
authors.lastname: Rinella
authors.forename: Heather
authors.initials: H
authors.lastname: Hill
authors.forename: Mark C
authors.initials: MC
authors.lastname: Wolff
authors.forename: Viola
authors.initials: V
authors.lastname: Schultze
authors.forename: Jang H
authors.initials: JH
authors.lastname: Han
authors.forename: Bruce
authors.initials: B
authors.lastname: Scharschmidt
authors.forename: Robert B
authors.initials: RB
authors.lastname: Belshe
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D004311:Double-Blind Method; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006508:Hepatitis Antibodies / Q000097:blood; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007115:Immunization Schedule; D008297:Male; D008875:Middle Aged; D011136:Polysorbates / Q000008:administration & dosage*; D013185:Squalene / Q000008:administration & dosage*; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D006508:Hepatitis Antibodies; C089950:MF59 oil emulsion; D011136:Polysorbates; D014761:Viral Hepatitis Vaccines; D013185:Squalene