title: Immunogenicity of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in nonresponders to licensed hepatitis B vaccine.
abstract: An additional one to three doses of hepatitis B vaccine are recommended for nonresponders to an initial standard three-dose series. We compared the safety and immunogenicity of an investigational hepatitis B surface antigen vaccine (HBsAg-1018) with a phosphorothioate oligodeoxyribonucleotide adjuvant that targets toll-like receptor-9 to a commercially available, alum-adjuvanted hepatitis B vaccine (HBsAg-Eng) in nonresponders to three previous doses (primary study) or to four to six previous doses (substudy) of HBsAg-Eng. Both vaccines were well tolerated, although HBsAg-1018 was associated with more injection-site tenderness (63.2% vs. 18.8%, p = 0.016 in the primary study and 81.8% vs. 15.4%, p = 0.003 in the substudy). No statistically significant differences in rates of seroprotection (anti-HBs concentration ≥ 10 mIU/mL) or geometric mean antibody concentrations were found in the primary study. In the substudy, a greater proportion of HBsAg-1018 recipients achieved an anti-HBs concentration ≥ 100 mIU/mL (54.5% vs. 8.3%, p = 0.027), and those responders had higher geometric mean antibody concentrations at 4 weeks (264 vs. 46.5 mIU/mL, p = 0.021) and 52 weeks (7.0 vs. 1.2 mIU/mL, p = 0.030) than HBsAg-Eng recipients. Although this study suggests that HBsAg-1018 may have improved immunogenicity in nonresponders to hepatitis B vaccine vaccination when compared with HBsAg-Eng, larger studies are required.
authors.affiliation: Canadian Center for Vaccinology; Dalhousie University, Capital Health, and the IWK Health Centre; Halifax, NS Canada.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ward
authors.forename: Marc
authors.initials: M
authors.lastname: Dionne
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Langley
authors.forename: Shelly A
authors.initials: SA
authors.lastname: McNeil
authors.forename: Bruce
authors.initials: B
authors.lastname: Smith
authors.forename: Donna
authors.initials: D
authors.lastname: Mackinnon-Cameron
authors.forename: William L
authors.initials: WL
authors.lastname: Heyward
authors.forename: J Tyler
authors.initials: JT
authors.lastname: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation / Q000276:immunology; D005260:Female; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D054735:Phosphorothioate Oligonucleotides / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology; D014611:Vaccination; D055815:Young Adult
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D054735:Phosphorothioate Oligonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
keywords: hepatitis B; hepatitis B vaccine; immunogenicity; immunostimulatory sequences; nonresponder; randomized trial