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

Vaccine. 2018 May 3;36(19):2604-2611. doi: 10.1016/j.vaccine.2018.03.067. Epub 2018 Apr 5.


Background: Hepatitis B virus infection remains an important global public health problem. Approved alum-adjuvanted vaccines are well tolerated but require three doses and have reduced immunogenicity in adults. A two-dose vaccine containing hepatitis B surface antigen combined with a novel, Toll-like receptor 9 agonist adjuvant (HBsAg-1018 [HEPLISAV-B®]) has demonstrated significantly higher seroprotection rates than a three dose vaccine.

Methods: A post hoc analysis compared the safety of HBsAg-1018 with HBsAg-Eng (Engerix-B®), in three randomized, observer-blinded, active-controlled, multi-center phase 3 trials in adults. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24.

Results: Post-injection reactions, adverse events, medically attended adverse events, and new-onset immune-mediated adverse events were balanced between vaccine groups. Anti-nuclear antibodies, anti-double stranded DNA antibodies, anti-neutrophil cytoplasmic antibodies, and antiphospholipid antibodies were balanced between groups. A transient increase in anti-beta2 glycoprotein 1 IgM was observed in the HBsAg-1018 group but was not associated with a thrombotic event. Serious adverse events and deaths were generally balanced between groups.

Conclusion: HBsAg-1018 had a similar safety profile to HBsAg-Eng. With improved immunogenicity and fewer doses over a shorter time, HBsAg-1018 has the potential to provide improved seroprotection and a significant public health benefit to adults 18 years of age or older.

Keywords: Hepatitis B vaccine; NCT00435812; NCT01005407; NCT02117934; Safety; Toll-like receptor 9.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Immunologic / pharmacology*
  • Adolescent
  • Adult
  • Aged
  • Cardiovascular Diseases / chemically induced*
  • Female
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B Vaccines / administration & dosage*
  • Hepatitis B Vaccines / adverse effects*
  • Humans
  • Male
  • Middle Aged
  • Toll-Like Receptor 9 / agonists*


  • Adjuvants, Immunologic
  • Engerix-B
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • TLR9 protein, human
  • Toll-Like Receptor 9