title: Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults.
abstract: BACKGROUND
  Many individuals do not respond to a three-dose series of hepatitis B vaccine (HBV) and most do not achieve a protective antibody response until after dose 2 or 3.
  
  
  METHODS
  Healthy, seronegative 18-28 year old adults were randomly assigned in equal numbers to receive two doses of the experimental vaccine (HBV-ISS without alum) (0, 8 weeks) and placebo (24 weeks) or Engerix-B (0, 8, 24 weeks). Adverse events were collected during the first week and at 4 weeks after each injection. Antibodies were measured 4 weeks after dose 1; before, 1 and 4 weeks after dose 2, and before, 1 and 4 weeks after dose 3 and at 1 year.
  
  
  RESULTS
  Ninety-nine participants were enrolled (65% female; mean age 22.6 years). 79% of HBV-ISS and 12% of Engerix-B recipients had a protective antibody response 4 weeks post dose 1 (geometric mean concentration [GMC] 23.0 and 1.87 mIU/mL, respectively). By 1 week post dose 2, 100% of HBV-ISS and 18% Engerix-B recipients had protective levels (GMC 1603 versus 2.40 mIU/mL). Rates of adverse events were low and similar in both groups; headache and fatigue were the most common systemic adverse events in up to 1/3 of both groups. Mild injection-site tenderness was more common after HBV-ISS than Engerix-B after both doses (74-77% compared to 34-58%; p<or=0.029).
  
  
  CONCLUSIONS
  Protective levels are achieved more quickly and after fewer doses of HBV-ISS than Engerix-B. HBV-ISS is well tolerated but associated with more mild injection-site tenderness than Engerix-B.
authors.affiliation: Clinical Trials Research Center, Dalhousie University, IWK Health Centre, 5850/5980 University Avenue, Halifax, NS, Canada B3K 6R8. scott.halperin@dal.ca
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.forename: Simon
authors.initials: S
authors.lastname: Dobson
authors.forename: Shelly
authors.initials: S
authors.lastname: McNeil
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Langley
authors.forename: Bruce
authors.initials: B
authors.lastname: Smith
authors.forename: Robyn
authors.initials: R
authors.lastname: McCall-Sani
authors.forename: Dan
authors.initials: D
authors.lastname: Levitt
authors.forename: Gary Van
authors.initials: GV
authors.lastname: Nest
authors.forename: Daniel
authors.initials: D
authors.lastname: Gennevois
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eiden
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D008297:Male; D009841:Oligonucleotides / Q000008:administration & dosage*; D013873:Thionucleotides / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D009841:Oligonucleotides; D013873:Thionucleotides