Immunogens consisting of oligosaccharides from the capsule of Haemophilus influenzae type b coupled to diphtheria toxoid or the toxin protein CRM197.
Haemophilus influenzae type b (Hib) capsular polysaccharide (PRP) was selectively hydrolyzed to reducing oligosaccharides, and the fraction containing 3-10 ribosylribitolphosphate repeating units (VS) was conjugated by reductive amination to diphtheria toxin (DTx), its nontoxic derivative CRM197 (Dcr), or diphtheria toxoid (DTd). Conjugate DTx-VS retained approximately 1% of native toxicity, which was eliminated by treatment with formalin. Immunization of rabbits with the conjugates elicited antibody (Ab) to PRP and to DTx but not to a model for the linkage determinant. Human adults given single subcutaneous injections had rises in serum Ab to PRP and in bactericidal activity in vitro; the Ab protected infant rats challenged with Hib. Adults had rises also in Ab to DTd, and these Ab protected rabbits against DTx. A series of two injections of the conjugates Dcr-VS and DTd-VS was tested in infants beginning at 19-23 mo of age. Rises in anti-PRP Ab after the primary resembled the rises after PRP vaccine. In contrast to PRP, the conjugates elicited large rises after the secondary vaccinations and a substantial IgG component. Development of bactericidal activity paralleled the rises in anti-PRP Ab. Secondary rises after Dcr-VS were higher than after DTd-VS. In infants 12-16 mo of age, Dcr-VS (but not DTd-VS) elicited strong primary and secondary Ab responses that included IgG and bactericidal activity. Both conjugates produced consistent rises in Ab to DTd.
D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001428:Bacterial Vaccines / Q000276:immunology*; D003429:Cross Reactions; D004167:Diphtheria Toxin / Q000276:immunology; D004168:Diphtheria Toxoid / Q000276:immunology; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007223:Infant; D009844:Oligosaccharides / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011817:Rabbits
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D004167:Diphtheria Toxin; D004168:Diphtheria Toxoid; D009844:Oligosaccharides; D011135:Polysaccharides, Bacterial