Effect of neonatal immunization with diphtheria and tetanus toxoids on antibody responses to Haemophilus influenzae type b conjugate vaccines.

We randomly assigned 150 newborn infants to receive diphtheria and tetanus toxoids (DT) or Hib oligosaccharide conjugate (HbOC) at birth to determine whether exposure to the Haemophilus influenzae type b (Hib) conjugate vaccines' carrier proteins would enhance immune responses to subsequent administrations of HbOC or PRP-tetanus toxoid conjugate (PRP-T) at 2, 4, and 6 months of age. Their antibody responses were compared with those of 100 children immunized with HbOC or PRP-T beginning at 2 months of age. No serious adverse reactions were associated with neonatal vaccination. Administration of HbOC at birth did not lead to earlier or higher antibody levels. Newborn immunization with DT did not prime children for enhanced antibody responses. Moreover, Hib antibody levels were lower in DT-primed children than in children immunized beginning at 2 months of age. Diphtheria antibody levels, but not tetanus antibody levels, were also lower in children immunized with DT at birth. We conclude that neonatal immunization with Hib conjugate vaccines is not a means to provide earlier protection against invasive Hib disease. Newborn DT administration does not enhance subsequent antibody responses to Hib conjugate vaccines, and may lead to suppression of Hib and diphtheria antibody responses.

Enhanced antibody responses in infants given different sequences of heterogeneous Haemophilus influenzae type b conjugate vaccines.

To evaluate the safety and immunogenicity of differing sequences of heterogeneous Haemophilus influenzae type b (Hib) conjugate vaccines, we randomly assigned 300 infants to one of six vaccination schedules. At 2, 4, and 6 months of age, subjects were given single or heterogeneous vaccines: Hib polysaccharide (PRP) conjugated to mutant diphtheria toxin (HbOC), PRP conjugated to outer-membrane protein of Neisseria meningitidis (PRP-OMP), or PRP conjugated to tetanus toxoid (PRP-T). No serious reactions were attributable to immunization with heterogeneous vaccines, and there were few significant differences in the rates of minor adverse reactions among groups. PRP-OMP was the only vaccine that induced an antibody response after the first dose, but significant booster responses were not seen after the second and third doses. Subjects given PRP-T vaccine responded well after two doses, but three doses of HbOC vaccine were needed for an equivalent antibody response. All the Hib vaccine schedules evaluated were immunogenic, and schedules initiated by PRP-OMP vaccine at 2 months of age, followed by two doses of either HbOC or PRP-T vaccine at 4 and 6 months of age, induced the highest antibody levels after each dose. Such schedules may be the best for protecting infants and children who are at greatest risk of having invasive Hib disease, such as American Indian children.