Background: HEPLISAV-B® [hepatitis B vaccine (recombinant), adjuvanted] uses a cytidine phospho-guanosine (CpG) oligonucleotide or 1018, a Toll-like receptor 9 agonist, as an adjuvant. Engerix-B® [hepatitis B vaccine (recombinant)], as well as other hepatitis B vaccines, use alum. HEPLISAV-B, a 2-dose vaccine given at Weeks 0 and 4, was recently approved for use in adults ≥18 years for the prevention of hepatitis B. Approval of HEPLISAV-B was based on three pivotal phase 3 noninferiority trials, comparing it with Engerix-B, a 3-dose vaccine given at Day 0, Day 30, and 6 months. Immunogenicity and safety results for these trials, HBV-10, HBV-16 and HBV-23, have been published previously; the safety of HEPLISAV-B was generally similar to Engerix-B.
Methods: The 3 randomized trials were observer-blinded and collectively included subjects aged 1870 years. Immunogenicity analysis based on antibody against hepatitis B surface antigen (anti-HBs) levels were based on per-protocol analysis. Presented here are reverse cumulative frequency plots of anti-HBs serum concentrations for the 3 trials.
Results: Across the trials, reverse cumulative frequency plots of anti-HBs concentrations showed a higher proportion (>90%) of HEPLISAV-B subjects developed a seroprotective antibody level (anti-HBs levels ≥10 mIU/mL) compared with Engerix-B subjects (80% ~90%). A higher proportion of HEPLISAV-B subjects had anti-HBs levels between 10 mIU/mL1,000 mIU/mL. While a higher proportion of Engerix-B subjects had anti-HBs levels >1,000 mIU/mL, a significantly higher proportion of Engerix-B subjects did not develop seroprotective antibody levels. The response curves indicate a more consistent immune response with a higher percentage of subjects achieving seroprotection with less variability for HEPLISAV-B compared to Engerix-B, which showed a more variable response and fewer subjects achieving seroprotection.
Conclusion: HEPLISAV-B, using a CpG adjuvant, results in a higher percentage of persons achieving seroprotection and produces a more uniform and consistent induction of protective antibody levels than Engerix-B, an alum-adjuvanted vaccine.
R. N. Hyer,
Dynavax Technologies Corporation: