Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age

Vaccine. 2012 Mar 28;30(15):2556-63. doi: 10.1016/j.vaccine.2012.01.087. Epub 2012 Feb 9.


Background: The currently licensed aluminum-hydroxide-adjuvanted hepatitis B vaccines require three doses over a 6-month period to achieve high rates of protection in adults. We compared tolerability and immunogenicity of two doses of an investigational hepatitis B vaccine using hepatitis B surface antigen adjuvanted with an immunostimulatory phosphorothioate oligodeoxyribonucleotide (HBV-ISS) to three doses of a licensed alum-adjuvanted vaccine (HBV-Eng).

Methods: In this randomized, observer-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 weeks or three doses of HBV-Eng at 0, 4, and 24 weeks. The primary immunogenicity endpoint was the seroprotection rate (antibody ≥ 10 mIU/mL) 8 weeks after the second dose of HBV-ISS compared to 4 weeks after the third dose of HBV-Eng.

Results: A total of 2415 participants were randomized in a ratio of 3:1 to HBV-ISS (n=1809) and HBV-Eng (n=606). The percentage of subjects exhibiting a seroprotective immune response at the primary time point was significantly higher (95.1%) for HBV-ISS than for HBV-Eng (81.1%). Superiority of the seroprotective rates for HBV-ISS was demonstrated at all time points measured. Geometric mean concentrations were also significantly higher in the HBV-ISS group at all time points measured except at week 28 (24 weeks post-second dose of HBV-ISS and 4 weeks post-third dose HBV-ISS) at which time the antibody concentrations were similar. Both vaccines were welltolerated although injection-site reactions were reported at a higher rate in HBV-ISS recipients.

Conclusions: A short, two-dose regimen of HBV-ISS induced a superior antibody response than a three-dose regimen of a licensed hepatitis B vaccine and was well tolerated.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Adolescent
  • Adult
  • Female
  • Hepatitis B / prevention & control*
  • Hepatitis B Antibodies / immunology
  • Hepatitis B Surface Antigens / administration & dosage
  • Hepatitis B Surface Antigens / adverse effects*
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / adverse effects*
  • Hepatitis B Vaccines / immunology*
  • Hepatitis B virus / immunology
  • Humans
  • Male
  • Middle Aged
  • Oligodeoxyribonucleotides / administration & dosage
  • Oligodeoxyribonucleotides / adverse effects*
  • Oligodeoxyribonucleotides / immunology*
  • Young Adult


  • Adjuvants, Immunologic
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Oligodeoxyribonucleotides
  • 1018 oligonucleotide