Safety and immunogenicity of Haemophilus influenzae type b polysaccharide and polysaccharide diphtheria toxoid conjugate vaccines in children 15 to 24 months of age.

To evaluate the safety and immunogenicity of the Haemophilus influenzae type b polysaccharide vaccine, PRP, and a new polysaccharide-diphtheria toxoid conjugate vaccine, PRP-D, a collaborative study was carried out in six centers in five states. Subjects were 585 infants 15 to 24 months of age. They were randomly assigned to receive a single dose of PRP or PRP-D vaccine. There were no significant differences in the rate of adverse reactions between the two vaccine groups. Minor local reactions occurred in 10.3% of PRP and 12.5% of PRP-D recipients, and fever in 27.4% of PRP and 23.8% of PRP-D recipients. All reactions resolved within 48 hours. Serum samples were obtained just before vaccination and after 1 month. Prevaccination antibody levels were similar for the PRP (0.035 micrograms/mL) and PRP-D (0.027 micrograms/mL) groups, with no differences in levels by age, sex, race, vaccine lot, or study site. Both groups had significant rises in geometric mean levels, but this difference was significantly greater for PRP-D (2.166 micrograms/mL) than for PRP (0.154 micrograms/mL). In addition, the percentage of responders as determined by three definitions (twofold titer rise, greater than 0.15 micrograms/mL, and greater than 1.0 micrograms/mL) was also significantly greater for PRP-D than PRP. In contrast to a marked age-related immunogenicity to PRP (P less than 0.001), there was no significant variation in immune response to PRP-D by age. PRP-D conjugate vaccine appears to be as safe and significantly more immunogenic than PRP vaccine for children vaccinated at 15 to 24 months of age.