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

Abstract

Background: Merck has developed a manufacturing process modification for RECOMBIVAX HB™. Three lots of modified process hepatitis B vaccine (mpHBV) were studied in a randomized, blinded trial to demonstrate similarity of the 3 lots of mpHBV and noninferiority to RECOMBIVAX HB™ (control vaccine) with regard to immunogenicity. 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 geometric mean titers (GMTs) and seroprotection rates (SPRs) (% of subjects with an anti-HBs titer ≥10 mIU/mL) were compared at Month 7. After each dose, injection-site adverse experiences (AEs) and oral temperature were recorded for 5 days; systemic AEs were recorded for 15 days.Results: Month 7 SPRs for the mpHBV groups ranged from 97.8 to 98.9% (98.2% for the mpHBV groups combined). The SPR for the control group was 98.5%. The estimated 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 AE, injection-site AEs, or systemic AEs were similar across the 4 vaccination groups. There were no serious AEs. 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.