Journal Article

Immunogenicity and safety of an investigational hepatitis B vaccine with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared to a licensed hepatitis B vaccine in healthy adults 40–70 years of age

Reisinger, Keith, Kyle, Michael, Janssen, Robert S., Kabongo, Martin L., Heyward, William L., Martin, J. Tyler, Davis, Matthew, Blumenau, Joseph, Bennett, Sean, Namini, Hamid

2013

Overview

•Phase 3 trial of investigational hepatitis B vaccine in adults 40–70years old.•2 doses of HBsAg-1018 demonstrated superior seroprotection to 3 doses of HBsAg-Eng.•HBsAg-1018 induced earlier seroprotection than HBsAg-Eng.•The safety profile of HBsAg-1018 was similar to that of HBsAg-Eng. The currently licensed hepatitis B vaccines have limitations including hyporesponsiveness in older adults, poor compliance, and the extended time for most persons to develop seroprotection (e.g. >6months). A vaccine containing HBsAg combined with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) has been developed to overcome these limitations. A Phase 3, multicenter, randomized, subject- and observer-blinded, active-controlled trial was conducted among healthy subjects 40–70years of age comparing the immunogenicity and safety of two doses of HBsAg-1018 at 0 and 4weeks to three doses of licensed hepatitis B vaccine, HBsAg-Eng, at 0, 4, and 24weeks. The primary immunogenicity endpoint was noninferiority of the seroprotection rate (SPR; % with anti-HBs≥10mIU/mL) of HBsAg-1018 compared to the SPR of HBsAg-Eng at 8 weeks following the last dose of vaccine. Conditional upon meeting noninferiority, superiority of HBsAg-1018 over HBsAg-Eng was assessed. Safety was compared between the two vaccines. At the primary endpoint, the SPR for the HBsAg-1018 group (90.0%) was superior to the SPR for the HBsAg-Eng group (70.5%) with an SPR difference of 19.5% (95% CI, 14.7%, 24.7%). At week 28 when the SPR peaked in the HBsAg-Eng group (72.8%), the SPR in the HBsAg-1018 group (94.8%) was significantly higher than in the HBsAg-Eng group. The SPR in the HBsAg-1018 group was significantly higher than in the HBsAg-Eng group at each study visit from week 4 through week 52. The safety profiles for the two vaccines were similar. When compared to the HBsAg-Eng three-dose regimen given at 0, 1, and 6months, HBsAg-1018 demonstrated superior seroprotection with only two doses at 0 and 1month. The safety profile of HBsAg-1018 was comparable to that of the licensed vaccine, HBsAg-Eng. HBsAg-1018 would provide a significant public health contribution toward the prevention of hepatitis B infection.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Adjuvants, Immunologic - administration & dosage / Adjuvants, Immunologic - adverse effects / Adult / Age / Aged / agonists / Allergy and Immunology / Applied microbiology / Biological and medical sciences / Compliance / Double-Blind Method / Drug-Related Side Effects and Adverse Reactions - epidemiology / Drug-Related Side Effects and Adverse Reactions - pathology / elderly / Female / Fundamental and applied biological sciences. Psychology / Health care / Healthy Volunteers / Hepatitis / hepatitis B / Hepatitis B - prevention & control / Hepatitis B Antibodies - blood / hepatitis B antigens / Hepatitis B Surface Antigens - administration & dosage / Hepatitis B Surface Antigens - immunology / Hepatitis B vaccine / Hepatitis B Vaccines - administration & dosage / Hepatitis B Vaccines - adverse effects / Hepatitis B Vaccines - immunology / Hepatitis B virus / Human viral diseases / Humans / immune response / Immunogenicity / Infections / Infectious diseases / Licenses / Male / Medical sciences / Microbiology / Middle Aged / Miscellaneous / Older people / Oligodeoxyribonucleotides - administration & dosage / Oligodeoxyribonucleotides - adverse effects / people / Population / Public health / Randomized trial / Safety / Toll-like receptor 9 / Toll-Like Receptor 9 - agonists / Toll-like receptor 9 agonist / Vaccination - methods / Vaccines / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) / Viral diseases / Viral hepatitis / Virology