Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults

Vaccine. 2018 Jan 29;36(5):668-674. doi: 10.1016/j.vaccine.2017.12.038. Epub 2017 Dec 27.


Background: Hepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke.

Methods: Phase 3 observer-blinded, randomized (2:1 HBsAg-1018 [HEPLISAV-B™]:HBsAg-Eng [Engerix-B®]), active-controlled trial in adults 18-70 years of age. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. The primary immunogenicity endpoint assessed the noninferiority of the seroprotection rate at week 28 in participants with type 2 diabetes mellitus. Secondary endpoints included seroprotection rates in the total trial population and by age, sex, body mass index, and smoking status.

Results: Among 8374 participants randomized, 961 participants in the per-protocol population had type 2 diabetes mellitus. In diabetes participants, the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0%, compared with 65.1% in the HBsAg-Eng group, with a difference of 24.9% (95% CI: 19.3%, 30.7%), which met the prospectively-defined criteria for noninferiority and statistical significance. In the total study per-protocol population (N = 6826) and each pre-specified subpopulation, the seroprotection rate in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group.

Conclusion: Two doses of HBsAg-1018, administered over 4 weeks, induced significantly higher seroprotection rates than three doses of HBsAg-Eng, given over 24 weeks, in adults with factors known to reduce the immune response to hepatitis B vaccines as well as in those without those factors. With fewer doses in a shorter time, and greater immunogenicity, HBsAg-1018 has the potential to significantly improve protection against hepatitis B in adults at risk for hepatitis B infection. Trial Registration Identifier: NCT02117934.

Keywords: Diabetes mellitus; Engerix-B; HEPLISAV-B; Hepatitis B vaccine; Toll-like receptor 9.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / immunology
  • Female
  • Hepatitis B / immunology*
  • Hepatitis B / prevention & control*
  • Hepatitis B Antibodies / blood
  • Hepatitis B Antibodies / immunology
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / adverse effects
  • Hepatitis B Vaccines / immunology*
  • Humans
  • Immunity, Innate
  • Immunogenicity, Vaccine*
  • Male
  • Middle Aged
  • Toll-Like Receptor 9 / agonists*
  • Young Adult


  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Toll-Like Receptor 9

Associated data