Safety and immunogenicity of Haemophilus influenzae-tetanus toxoid conjugate vaccine given separately or in combination with a three-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine for the first four doses

The purpose of this randomized, controlled trial was to assess the safety and immunogenicity of a three-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine given either separately or combined as a single injection with a Haemophilus influenzae type b-tetanus toroid conjugate vaccine. A total of 180 infants were immunized at 2, 4, and 6 months of age; 129 were given a booster dose at 16-19 months of age, Vaccine-associated adverse events were similar whether the vaccines were combined as a single injection or given separately. There were no differences in levels of antibodies to Bordetella pertussis antigens (pertussis toroid, filamentous hemagglutinin, and pertactin), diphtheria toroid, or the three poliovirus types. The tetanus antitoxin level after the primary three-dose series was higher in recipients of the combined vaccine (2.37 IU/mL) than in recipients of the separate injections (1.32 IU/mL; two-sided P = .0001). In contrast, combined vaccine recipients had lower levels of antibody to H. influenzae type b polysaccharide after the third dose (1.57 mu g/mL) than did those given separate injections (3.22 mu g/mL; two-sided P = .0026). The antibody levels were not significantly different before or 1 month after the booster dose (32.9 mu g/mL vs; 47.8 mu g/mL, respectively; two-sided P = .07). We conclude that the vaccines were immunogenic and well tolerated. Despite lower levels of antibody to the H. influenzae type b polysaccharide after the primary three-dose series, mixing of the vaccines in a single syringe likely induced immunologic priming, as suggested by the high antibody levels after the booster dose.