A randomized, prospective field trial of a conjugate vaccine in the protection of infants and young children against invasive Haemophilus influenzae type b disease.

BACKGROUND Haemophilus influenzae type b is the leading cause of invasive bacterial disease in young children. The capsular polysaccharide vaccine does not protect children at greatest risk (those under the age of 18 months), but a polysaccharide-protein conjugate vaccine has proved to be more immunogenic in this age group. METHODS We enrolled 114,000 infants in Finland in an open, prospective, randomized trial of a H. influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (polyribosylribitol phosphate-diphtheria toxoid [PRP-D]). Children born on odd-numbered days were vaccinated at the ages of 3, 4, 6, and 14 to 18 months; those born on even-numbered days formed the control group and received the same vaccine at the age of 24 months. RESULTS After three doses of the vaccine there were 4 cases of verified bacteremic H. influenzae type b disease in the group receiving early vaccination, as compared with 64 cases in the control group, between the ages of approximately 7 and 24 months. The protective efficacy of the vaccine was thus 94 percent (95 percent confidence interval, 83 to 98). No serious adverse effects were reported. The immune response to the conjugate vaccine was characteristic of a T-cell-dependent response when studied in a cohort of 120 infants. The primary immunization series resulted in a geometric mean concentration of anticapsular antibody of 0.53 micrograms per milliliter at the age of seven months, and the fourth dose evoked an anamnestic response, with a mean antibody concentration of 45.22 micrograms per milliliter. CONCLUSIONS A new conjugate vaccine consisting of the capsular polysaccharide of H. influenzae type b covalently linked to a protein carrier (PRP-D), administered to infants beginning at the age of 3 months, is highly effective in protecting young Finnish children (7 to 24 months old) against invasive H. influenzae type b infections.