Studies on a Hib-tetanus toxoid conjugate vaccine: effects of co-administered tetanus toxoid vaccine, of administration route and of combined administration with an inactivated polio vaccine.

A freeze-dried tetanus toxoid (T) conjugated Haemophilus influenzae type b (Hib) vaccine, was reconstituted in either diphtheria toxoid (D), DT or a combined DT and inactivated polio vaccine (IPV), and administered in an open randomized trial either intramuscularly (i.m. ) or subcutaneously (s.c.) to 287 Swedish infants at three, five and 12 months of age. When not included in the mixture, IPV was administered s.c. at a separate site. The geometric mean concentrations of Hib antibodies after primary and booster vaccinations were 1.0 and 11.6 microg/ml, respectively, with no differences related to co-administration of the carrier protein T. Antibodies against T were induced by the T conjugated Hib vaccine (Hib-T) alone in 69/95 infants aged six months, and in 87/93 children aged 13 months, although infants receiving both Hib-T and T had significantly higher concentrations. Antibody responses to Hib, D, T or polio were not negatively influenced by administration route or by mixing with IPV, except that the mixed vaccine DT-IPV induced lower anti-polio GM titers after primary vaccination than did separate IPV. More local reactions were induced by the s.c. than by the i.m. route (P-values from 0.001 to 0.01). Slight increases in rates of local reactions and febrile events (>/=38 degrees C) occurred by order of dose. The low Hib antibody concentrations after the first two doses in this and other Swedish studies are unlikely to be of clinical relevance. The tetanus antibody response from T as a carrier protein alone was not sufficient for basic tetanus immunization, but should be considered in future use of additional T conjugated vaccines.