Safety and immunogenicity of different two-dose regimens of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in healthy young adults

Vaccine. 2012 Aug 3;30(36):5445-8. doi: 10.1016/j.vaccine.2012.05.074. Epub 2012 Jun 13.

Abstract

Background: Previous studies have shown that two doses of an investigational hepatitis B vaccine consisting of hepatitis B surface antigen combined with an immunostimulatory phosphorothioate oligodeoxyribonucleotide adjuvant (HBV-ISS) given 8 weeks apart provides seroprotection sooner than 3 doses of a licensed hepatitis B vaccine over 24 weeks. A more rapid schedule with a 4-week interval could provide earlier protection and potentially greater compliance.

Methods: In this randomized, double-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 or 0 and 8 weeks; saline placebo was given at week 8 for the 0-4 schedule and at week 4 for the 0-8 schedule). Adverse events were collected after each dose. Antibodies were measured at 0, 4, 8, 12, and 32 weeks.

Results: Participants were randomized to the 0-4 (n=18) or 0-8 (n=23) weeks schedule. Rates of adverse events were similar in the two groups after the HBV-ISS injections regardless of the schedule, but more frequent than after the placebo injections. By 4 weeks post-dose-2, 94.1% of 0-4 and 100% of 0-8 recipients had protective antibody levels; geometric mean concentrations were 244 mIU/mL and 3217 mIU/mL respectively. By 32 weeks, the difference in antibody concentration had decreased (GMC 439 mIU/mL vs. 863 mIU/mL, respectively; p=0.04).

Conclusions: A 0-4 weeks, two-dose regimen of HBV-ISS was well-tolerated and induced an antibody response that was similar to a 0-8 weeks schedule.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adult
  • Female
  • Hepatitis B Antibodies / immunology
  • Hepatitis B Surface Antigens / chemistry
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / adverse effects*
  • Hepatitis B Vaccines / immunology*
  • Humans
  • Male
  • Oligodeoxyribonucleotides / administration & dosage*
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / immunology
  • Phosphorothioate Oligonucleotides / administration & dosage
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Oligodeoxyribonucleotides
  • Phosphorothioate Oligonucleotides