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 a nd immunogenicity of a three-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine giv en either separately or combined as a single injection with a Haemophilus i nfluenzae type b-tetanus toroid conjugate vaccine. A total of 180 infants w ere immunized at 2, 4, and 6 months of age; 129 were given a booster dose a t 16-19 months of age, Vaccine-associated adverse events were similar wheth er the vaccines were combined as a single injection or given separately. Th ere were no differences in levels of antibodies to Bordetella pertussis ant igens (pertussis toroid, filamentous hemagglutinin, and pertactin), diphthe ria toroid, or the three poliovirus types. The tetanus antitoxin level afte r the primary three-dose series was higher in recipients of the combined va ccine (2.37 IU/mL) than in recipients of the separate injections (1.32 IU/m L; 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, r espectively; two-sided P = .07). We conclude that the vaccines were immunog enic and well tolerated. Despite lower levels of antibody to the H. influen zae type b polysaccharide after the primary three-dose series, mixing of th e vaccines in a single syringe likely induced immunologic priming, as sugge sted by the high antibody levels after the booster dose.