Functional activities of human antibody induced by the capsular polysaccharide or polysaccharide-conjugate vaccines against Haemophilus influenzae type b

Abstract

To determine the in vitro and in vivo activity of human antibody induced by different Haemophilus influenzae type b (Hib) vaccines, pooled human antisera obtained from adults immunized with either polyribosyl ribitol phosphate (PRP) or PRP-conjugated with diphtheria toxoid (PRP-D) vaccines were evaluated for opsonic and protective activity against Hib. In vitro, opsonophagocytic studies revealed that PRP-D induced antisera were approximately 2.5-fold more effective than PRP-induced antisera in supporting neutrophil-mediated killing of an Hib strain. In vivo studies using the infant rat model or Hib disease revealed that the decay of PRP antibody was similar with PRP or PRP-D induced antisera in unchallenged rats. However, in infant rats challenged with Hib, the PRP induced antibody decayed more rapidly than the PRP-D induced antibody as shown by significantly shorter half-life of the former. The protective efficacy was significantly greater with the PRP-D induced antisera than with the PRP induced antisera. This finding was shown by the significantly lower incidence of bacteraemia and the 5-fold lower dose of antibody required for 50% protection against bacteraemia in rats receiving the PRP-D induced antisera. The findings suggest that antibody to PRP induced by PRP-D vaccine is more opsonic and protective against Hib, and also decays more slowly in infant rats challenged with Hib than does antibody induced by PRP vaccine. Further studies are needed to elucidate the reason(s) for this difference in functional activity and in half-life of PRP antibody induced by PRP or by PRP-D vaccines.