Immunogenicity of four Haemophilus influenzae type b conjugate vaccines in 17-to 19-month-old children

Objective: To compare the immunogenicity of four Haemophilus influenzae type b (Hib) conjugate vaccines in different populations of 17-to 19-month-old children in the United States. Design: Four immunogenicity trials with sera were assayed in one laboratory. Trials 1 and 2 each compared one vaccine in two regions, and trials 3 and 4 were randomized comparisons of multiple vaccines within a region. Subjects: A convenience sample of 313 healthy children recruited from pediatric practices in Minneapolis, Minn., Dallas and Houston, Tex., and Sellersville, Pa. Measurements and results: Children with prevaccination antibody >0.15 μg/ml showed higher antibody responses to vaccination than children with <0.15 μg/ml (p<0.001). Among the former, there were no significant differences in antibody response to vaccination with the different conjugates within any of the trials. Among children with <0.15 μg/ml of antibody before vaccination, there were no significant differences in the geometric mean antibody responses of children in trial 1 vaccinated with polyrbosylribitol phosphate-diphtheria toxoid (PRP-D) in Dallas or in Minneapolis, or of children in trial 3 in Dallas randomly assigned to receive Hib oligosaccharide-CRM₁₉₇ (HbOC) or PRP-D. In contrast, in trial 2, children given PRP-tetanus toxoid (PRP-T) in Pennsylvania had a significantly higher geometric mean antibody response than children given PRT-T in Houston (13.5 vs 3.0 μg/ml; p=0.005). In trial 4 in Minneapolis, the geometric mean antibody response was highest in children randomly assigned to receive PRP-outer membrane protein (OMP) (9.3 μg/ml), followed by PRP-D (5.0 μg/ml) and HbOC (2.3 μg/ml) (PRP-OMP vs HbOC; p=0.005). In all four trials, IgG1 responses predominated compared with IgG2 responses. Conclusions: All four conjugate vaccines are immunogenic in children 17 to 19 months of age. However, the magnitude of the anticapsular antibody response varied by vaccine type, the level of antibody in prevaccination sera, and geographic location.