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

Vaccine. 2013 Nov 4;31(46):5306-13. doi: 10.1016/j.vaccine.2013.05.067. Epub 2013 May 30.

Abstract

Background: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) infection and patients with chronic kidney disease (CKD) are commonly hyporesponsive to HBV vaccines. Current recommendations for CKD patients are to utilize 4 double-doses (2×20 mcg HBsAg) of a licensed hepatitis B vaccine (HBsAg-Eng).

Methods: An observer-blind, randomized, active-controlled, parallel group, multicenter trial was conducted among 521 patients 18-75 years of age with CKD, comparing 3 single doses of an investigational hepatitis B vaccine (20 mcg rHBsAg+3000 mcg 1018, a toll-like receptor 9 agonist) given at 0, 4, and 24 weeks to 4 double-doses of HBsAg-Eng (2×20 mcg rHBsAg+500 mcg alum) given at 0, 4, 8, and 24 weeks (total of 8 injections). Participants were followed for 1 year.

Results: Among 467 participants in the modified intent-to-treat population, at the primary endpoint at week 28, the seroprotection rate (SPR: % with anti-HBs≥10mIU/mL) in the HBsAg-1018 group (89.9%) met criteria for noninferiority and superiority to the SPR in the HBsAg-Eng group (81.8%). At week 28, the percentage of participants with anti-HBs≥100mIU/mL in the HBsAg-1018 group (73.6%) was significantly higher than in the HBsAg-Eng group (63.2%). In addition, the geometric mean concentration of anti-HBs in the HBsAg-1018 group (587.1mIU/mL) was significantly higher than in the HBsAg-Eng group (156.5mIU/mL). At weeks 8 and 12 after the first study injection, SPRs in the HBsAg-1018 group were significantly higher than in the HBsAg-Eng group. At 52 weeks, the immune response to HBsAg-1018 remained higher than to HBsAg-Eng. HBsAg-1018 was generally well tolerated and had a similar safety profile to HBsAg-Eng.

Conclusion: In CKD patients, 3 doses of HBsAg-1018 induced significantly higher seroprotection, earlier seroprotection, and more durable seroprotection than 4 double doses of HBsAg-Eng.

Trial registration: ClinicalTrials.gov NCT00985426.

Keywords: Hepatitis B vaccine; Randomized trial; Toll-like receptor 9.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects*
  • Adolescent
  • Adult
  • Aged
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Hepatitis B / prevention & control*
  • Hepatitis B Antibodies / blood
  • Hepatitis B Surface Antigens / administration & dosage
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / adverse effects*
  • Hepatitis B Vaccines / immunology*
  • Humans
  • Male
  • Middle Aged
  • Oligodeoxyribonucleotides / administration & dosage
  • Oligodeoxyribonucleotides / adverse effects*
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / immunology
  • Single-Blind Method
  • Toll-Like Receptor 9 / agonists
  • Vaccination / methods
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Oligodeoxyribonucleotides
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • 1018 oligonucleotide

Associated data

  • ClinicalTrials.gov/NCT00985426