title: Effect of immunity to the carrier protein on antibody responses to Haemophilus influenzae type b conjugate vaccines.
abstract: The anticapsular antibody responses to some Haemophilus influenzae type b (Hib) conjugate vaccines may be enhanced by prior or simultaneous administration of the carrier protein used in the conjugate. Currently, there are two Hib conjugate vaccines licensed in the USA for use in infants beginning at 2 months of age: Hib polysaccharide coupled to an outer membrane protein complex of Neisseria meningitidis (PRP-OMPC), and Hib oligosaccharides conjugated to CRM197, a non-toxic mutant diphtheria toxin (HbOC). The PRP-OMPC conjugate vaccine is immunogenic in infant monkeys and infant humans in the absence of carrier priming or additional carrier vaccination. The mechanism responsible for this immunogenicity is unknown but may relate to the adjuvanticity of the OMPC carrier. In contrast, data from infant rhesus monkeys and infant humans suggest that there may be a need for vaccination with diphtheria toxoid in order to maximize anti-PRP antibody responses to the HbOC conjugate. In addition, immunization with HbOC alone appears to be insufficient to elicit an antibody response to diphtheria toxoid. Thus, the need for additional vaccination with diphtheria toxoid in order to generate consistent anti-PRP antibody responses to HbOC may be a result of failure of the CRM197 protein carrier to elicit T-cell help. In infants in whom diphtheria-tetanus-pertussis (DTP) vaccination is deferred because of medical contraindications, vaccination with the PRP-OMPC conjugate would appear to be preferable to HbOC because of the ability of the former to elicit antibody responses in the absence of diphtheria toxoid vaccination.
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis Children's Hospital, MO 63110.
authors.forename: D M
authors.initials: DM
authors.lastname: Granoff
authors.forename: M H
authors.initials: MH
authors.lastname: Rathore
authors.forename: S J
authors.initials: SJ
authors.lastname: Holmes
authors.forename: P D
authors.initials: PD
authors.lastname: Granoff
authors.forename: A H
authors.initials: AH
authors.lastname: Lucas
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D016667:Bacterial Capsules; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000276:immunology; D018073:Haemophilus Vaccines; D006193:Haemophilus influenzae / Q000145:classification / Q000276:immunology*; D006801:Humans; D007223:Infant; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D004168:Diphtheria Toxoid; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; C044237:Haemophilus influenzae type b polysaccharide vaccine; C052180:Haemophilus influenzae type b-polysaccharide vaccine-diphtheria toxoid conjugate; C061964:Haemophilus influenzae-type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic; C061963:HibTITER protein, Haemophilus influenzae