Safety, tolerability and immunogenicity of a recombinant hepatitis B vaccine manufactured by a modified process in healthy young adults

Background: Merck has developed a manufacturing process modification for RECOMBIVAX HB (TM). Three lots of modified process hepatitis B vaccine (mpHBV) were studied in a randomized, blinded trial to demonstrate similarity of the three lots of mpHBV and noninferiority to RECOMBIVAX HBTM (control vaccine) with regard to immunogenicity. Results: Month 7 SPRs for the mpHBV groups ranged from 97.8 to 98.9% (98.2% for the mpHBV groups combined). The seroprotection rate (SPR) for the control group was 98.5%. The estimated geometric mean titer (GMT) was 1761 mIU/mL for the mpHBV groups combined and 1108 mIU/mL for the control group. The GMT ratio (mpHBV/control) was 1.6 [95% confidence interval (CI): 1.2 to 2.1], indicating superiority of mpHBV compared with control. The percentages of subjects reporting any adverse experience (AE), injection-site AEs, or systemic AEs were similar across the four vaccination groups. There were no serious AEs. Methods: Healthy 20-to 35-year-old subjects (N = 860) received a 1-mL intramuscular dose [10 mcg hepatitis B surface antigen (HBsAg)] of mpHBV from 1 of 3 lots or control at Day 1, and Months 1 and 6. Serum antibody to HBsAg (anti-HBs) was assayed Predose 1 and 1 month Postdose 3 (Month 7) using a quantitative hepatitis B antibody assay (Ortho VITROS ECi assay). Anti-HBs GMTs and SPRs (% of subjects with an anti-HBs titer >= 10 mIU/mL) were compared at Month 7. After each dose, injection-site AEs and oral temperature were recorded for 5 days; systemic AEs were recorded for 15 days. Conclusions: The SPRs for the mpHBV groups and the control group were high; responses were consistent across the mpHBV groups. The mpHBV and control vaccines were generally well tolerated.