Immunogenicity and safety of an investigational hepatitis B vaccine with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in patients with chronic kidney disease and type 2 diabetes mellitus

Vaccine. 2015 Feb 11;33(7):833-7. doi: 10.1016/j.vaccine.2014.12.060. Epub 2015 Jan 6.


Background: Many patients with chronic kidney disease (CKD) are hyporesponsive to currently licensed alum-adjuvanted hepatitis B vaccines, including Engerix-B(®) (HBsAg-Eng). Seroprotection rates (SPRs) are further reduced in CKD patients with diabetes mellitus. Three doses of an investigational hepatitis B vaccine (HBsAg-1018) that uses a Toll-like receptor 9 agonist demonstrated superior SPRs to 4 double doses of HBsAg-Eng in a large phase 3 trial of CKD patients.

Methods: A prespecified subgroup analysis of immunogenicity was conducted in CKD participants with type 2 diabetes in the phase 3 trial.

Results: In 328 participants, the peak SPR in the HBsAg-1018 group met criteria for noninferiority and superiority to the peak SPR in the HBsAg-Eng group. The peak geometric mean concentration of antibody against hepatitis B surface antigen in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group.

Conclusion: HBsAg-1018 induced significantly higher seroprotection than HBsAg-Eng in CKD patients with diabetes.

Keywords: CKD; Hepatitis B vaccine; NCT00985426; Toll-like receptor 9; Type 2 diabetes.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Adolescent
  • Adult
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / immunology*
  • Female
  • Hepatitis B / prevention & control*
  • Hepatitis B Antibodies / immunology
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B Vaccines / adverse effects*
  • Hepatitis B Vaccines / immunology*
  • Hepatitis B Vaccines / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / immunology*
  • Toll-Like Receptor 9 / agonists*
  • Young Adult


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