Phase I study of the immunogenicity and safety of conjugated Hemophilus influenzae type b vaccines in the elderly

Abstract

In infants, vaccines consisting of a carrier protein conjugated to the bacterial capsular polysaccharide (PRP) are far more protective against Hemophilus influenzae type b (Hib) disease than unconjugated PRP. To determine the tolerability and immunogenicity of Hib conjugate vaccines in the elderly, we vaccinated 30 volunteers, aged 69–84 years, with either PRP conjugated to an outer membrane protein complex (PRP-OMP), or PRP oligomers conjugated to CRM 197, a nontoxic, mutant diphtheria toxin (HbOC). Prior to vaccination, 40% of subjects had serum anti-PRP antibody levels <1.0 μg ml −1. Four weeks following vaccination, all subjects had concentrations >1.0 μg ml −1, a level generally considered to be protective. The post-vaccination geometric mean concentrations were 35.5 and 50.1 μg ml −1 for the PRP-OMP and HbOC groups, respectively (0.05< P<0.10). Subjects in the HbOC group, but not the PRP-OMP group, showed, on average, ten fold increases in IgG antibody to diphtheria toxoid after conjugate vaccination. Side-effects of vaccination were mild except in one subject given HbOC, who developed extensive erythema and swelling of the injected arm.