Clinical Comparison of the Haemophilus influenzae Type B Polysaccharide-Diphtheria Toxoid and the Oligosaccharide–CRM197 Protein Vaccines in Infancy

Abstract

To compare two Haemophilus influenzae type B (HiB) conjugate vaccines, a polysaccharide-diphtheria toxoid conjugate (PRP-D) vaccine and an oligosaccharide-CRM197 protein conjugate (HBOC [PRP-CRM]) vaccine, in the same population. One hundred twenty-five thousand infants were randomized to receive the PRP-D or HBOC vaccine. Primary immunization consisted of two doses of either vaccine administered at 4 and 6 months and a booster dose was given at 14 to 18 months. Protection was assessed by recording episodes of invasive disease with HiB isolated from the blood or another normally sterile body site. One thousand thirty-six child health care centers in Finland. Infants born in Finland during the 24-month period from 1987 to 1989. Each vaccine dose was injected intramuscularly in a volume of 0.5 mL. At the same time, a separate site was injected with the diphtheria and tetanus toxoids and pertussis vaccine at 4 months of age, with inactivated poliovirus vaccine at 6 months of age, and with measles-mumps-rubella vaccine at 14 to 18 months of age. The mean anticapsular antibody concentration 1 month after the second dose was 0.63 micrograms/mL and 4.32 micrograms/mL in the PRP-D and HBOC vaccine recipients, respectively. The booster dose resulted in a high antibody concentration: 33.3 micrograms/mL and 58.3 micrograms/mL for PRP-D and HBOC vaccine recipients, respectively. At 36 months of age, the antibody concentration declined to 2.5 micrograms/mL and 5.6 micrograms/mL for PRP-D and HBOC vaccine recipients, respectively. After two doses of the vaccine, there were five episodes (39 were expected based on historical controls) of invasive HiB disease in the PRP-D group and two episodes (35 were expected) in the HBOC group. Hence, an 87% (95% confidence limit [CL], 69, 96) protection rate in the PRP-D group and a 95% (95% CL, 76, 99) protection rate in the HBOC group were achieved. No episodes occurred after the booster dose in either group. Both the PRP-D and HBOC vaccines are safe and effective. A two-dose primary vaccination schedule seems appropriate, at least in circumstances prevailing in Finland and probably in other areas with similar epidemiological effects of HiB disease.