Several Haemophilus influenzae type b vaccines have been licensed and recommended for administration to children in the United States. These vaccines have consisted of purified polyribosylribitol-phosphate (PRP), the capsular polysaccharide of H influenzae type b,1 alone or covalently bound to one of several carrier proteins. Two of these saccharide-protein conjugate vaccines are now licensed, a polysaccharide-diphtheria toxoid conjugate (PRP-D)2 and an oligosaccharide-mutant diphtheria toxin conjugate (HbOC).3 Two others, a polysaccharide- Neisseria meningitidis outer membrane protein conjugate (PRP-OMPC)4 and a polysaccharide-tetanus toxoid conjugate (PRP-T),5 are currently in clinical trials.
One concern with the use of PRP vaccine was the suggestion that the incidence of invasive disease caused by H influenzae type b in the immediate period after immunization might be increased; this idea was supported by evidence from several sources. In a case-control study of the efficacy of PRP vaccine, Black et al6 found that 4 children were hospitalized for invasive disease within 1 week of immunization, a rate of invasive disease 6.4 times greater (95% confidence interval [CI], 2.1 to 19.2) than the background rate in unvaccinated children. In Minnesota, the relative risk for invasive disease in the first week after immunization was 6.2 (95% CI, 0.6 to 45.9),7 and the results of a study conducted by the Centers for Disease Control in six areas of the United States revealed a 1.8-fold (95% CI, 0.3 to 10.2) increase in the occurrence of invasive disease caused by H influenzae type b in the first week after immunization.8 Moreover, among 16 cases of disease caused by H influenzae type b occurring within 14 days of immunization that were passively reported to the FDA,9 10 were clustered within the first 72 hours.
Qualitative and quantitative analyses of the antibody response elicited by Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugates in adults with IgG subclass deficiencies and frequent infections
