Safety and immunogenicity of a combination diphtheria-tetanus toxoids-acellular pertussis-hepatitis B vaccine administered at two, four and six months of age compared with monovalent hepatitis B vaccine administered at birth, one month and six months of age

OBJECTIVE: To evaluate the safety and immunogenicity of diphtheria-tetanus toxoids-acellular pertussis (DTPa)-hepatitis B (HepB) combination vaccine given at 2, 4 and 6 months of age compared with monovalent HepB vaccine given at birth, 1 month and 6 months of age and DTPa vaccine given at 2, 4 and 6 months of age. METHODS: Healthy infants were randomized to receive a combination DTPa-HepB vaccine (diphtheria and tetanus toxoids, acellular pertussis antigens and hepatitis B surface antigen), concomitantly with type b and oral poliovirus vaccines at 2, 4 and 6 months of age (Group 1) or HepB vaccine given at birth, 1 month and 6 months of age and DTPa, type b and oral poliovirus vaccines given at 2, 4 and 6 months of age (Group 2). Antibody responses were evaluated at birth, 2 months and 7 months of age. Safety was evaluated after each immunization using diary cards and parental interviews. RESULTS: One month after the third dose (7 months of age), the geometric mean concentration of antibody to hepatitis B surface antigen was approximately 3.5-fold higher in Group 2 than in Group 1 infants (3643 and 1052 mIU/ml, respectively; < 0.001). Nevertheless the rates of seroprotection to HepB (antibody to hepatitis B surface antigen > or =10 mIU/ml) in Groups 1 and 2 were similar, 99 and 100%, respectively. Also the postvaccination geometric mean concentrations and rates of seroprotection or vaccine response to all of the other vaccine antigens evaluated were similar or greater in Group 1 than in Group 2. The rates of adverse events were similar between the two groups, with fussiness and soreness at any injection site reported most frequently. CONCLUSIONS: The DTPa-HepB combination vaccine was safe and immunogenic when given to infants at 2, 4 and 6 months of age. Equivalent rates of seroprotection to hepatitis B were achieved despite a reduction of the interval between the second and third doses from 5 months in Group 2 to 2 months in Group 1. Hepatitis B-containing combination vaccines should reduce the number of vaccine injections required in childhood and maintain excellent seroprotection against multiple pathogens.