We performed a double-blind, randomized trial to compare the immunogenicity and reactogenicity of four conjugate Haemophilus influenzae type b
vaccines given to infants 2, 4, and 6 months of age. Adverse reactions attributable to the
vaccines were few and minor. The rates of systemic reactions did not differ among the various
vaccines and were similar to those seen among children receiving conventional
diphtheria-tetanus-pertussis vaccine. However, the four conjugate H. influenzae type b
vaccines differed markedly in ability to stimulate antibody production. Mean antibody levels after three
injections of polyribosylribitol
phosphate conjugated with mutant
diphtheria protein (PRP-CRM) or polyribosylribitol
phosphate conjugated with
tetanus toxoid (
PRP-T) were 3.08 micrograms/ml and 3.64 micrograms/ml, respectively, significantly higher than those after the use of polyribosylribitol
phosphate conjugated with outer-
membrane protein of Neisseria meningitidis (PRP-OMP) (1.14 micrograms/ml) or polyribosylribitol
phosphate conjugated with
diphtheria toxoid (
PRP-D) (0.28 microgram/ml). Only PRP-OMP produced a clinically pertinent elevation in antibody level after two
injections (0.84 microgram/ml); the third injection of PRP-OMP produced a modest but statistically significant further elevation in mean antibody level (1.14 micrograms/ml). Only 29% of infants receiving
PRP-D had antibody levels of 1 micrograms/ml, compared with 55%, 75%, and 83% of those receiving PRP-OMP, PRP-CRM, and
PRP-T, respectively. We conclude that all four
vaccines are safe and that all but
PRP-D appear appropriate for use in a primary immunization series during infancy. The unique serologic response to PRP-OMP offers both advantages and disadvantages in comparison with PRP-CRM and
PRP-T.