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

• Published in: Vaccine Vol. 31; no. 46; pp. 5300 - 5305
• Main Authors: Heyward, William L., Kyle, Michael, Blumenau, Joseph, Davis, Matthew, Reisinger, Keith, Kabongo, Martin L., Bennett, Sean, Janssen, Robert S., Namini, Hamid, Martin, J. Tyler
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 04.11.2013; Elsevier; Elsevier Limited
• Subjects: 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; United States > US; Hepatitis B vaccine; Toll-like receptor 9 agonist; Randomized trial; Hepatitis B surface antigen; Orthohepadnavirus; Hepatic disease; Vaccine; Toll like receptor 9; Infection; Virus; Viral hepatitis B; Viral hepatitis A; Immunogenicity; Hepadnaviridae; Viral disease; Immunological adjuvant; Digestive diseases; Hepatitis B virus; Age
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2013.05.068

•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.