title: Variable region expression in the antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-protein conjugates. Description of a new lambda light chain-associated idiotype and the relation between idiotype expression, avidity, and vaccine formulation. The Collaborative Vaccine Study Group.
abstract: Haemophilus influenzae b polysaccharide (Hib PS)-protein conjugate vaccines differ chemically and immunologically. To determine whether anti-Hib PS variable region expression might differ according to vaccine formulation, infants were vaccinated at 2, 4, and 6 mo of age with Hib PS coupled to either meningococcal outer membrane protein complex (Hib PS-OMPC) or tetanus toxoid (Hib PS-T), or Hib PS oligomers coupled to a mutant diphtheria toxin (Oligo-CRM). Two anti-Hib PS idiotypes were measured in sera obtained after the third injection: HibId-1, expressed by anti-Hib PS antibodies having the kappa II-A2 variable region, and HibId-2, a newly defined cross-reactive idiotype associated with a subset of anti-Hib PS antibodies having lambda VII variable regions. HibId-1 was present in 33, 68, and 64% of infants given either Hib PS-OMPC, Oligo-CRM, or Hib PS-T, respectively (P < 0.001). The respective values for HibId-2 were 47, 18, and 10% (P = 0.001). Subjects who were vaccinated with Hib PS-OMPC or Hib PS-T and who produced detectable HibId-1-positive antibody, had significantly higher mean antibody avidity than subjects who did not produce HibId-1 positive antibodies. In contrast, Oligo-CRM evoked high avidity anti-Hib PS antibodies, irrespective of the idiotypic profile. These findings indicate fundamental differences in both variable region content and antibody quality elicited by different Hib PS conjugate vaccines.
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, Missouri 63110.
authors.forename: D M
authors.initials: DM
authors.lastname: Granoff
authors.forename: P G
authors.initials: PG
authors.lastname: Shackelford
authors.forename: S J
authors.initials: SJ
authors.lastname: Holmes
authors.forename: A H
authors.initials: AH
authors.lastname: Lucas
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage*; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D004168:Diphtheria Toxoid / Q000008:administration & dosage*; D005260:Female; D018073:Haemophilus Vaccines; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000097:blood*; D007223:Infant; D008297:Male; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage*; D013745:Tetanus Toxoid / Q000008:administration & dosage*; D014614:Vaccines, Synthetic / Q000008:administration & dosage*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D004168:Diphtheria Toxoid; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; C052180:Haemophilus influenzae type b-polysaccharide vaccine-diphtheria toxoid conjugate; C061964:Haemophilus influenzae-type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine; D007135:Immunoglobulin Variable Region; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic