Variable region expression in the antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-protein conjugates. Description of a new λ light chain-associated idiotype and the relation between idiotype expression, avidity, and vaccine formulation

D. M. Granoff, P. G. Shackelford, S. J. Holmes, T. V. Murphy, Michael T. Osterholm, E. L. Anderson, R. B. Belshe, J. Esbenshade, M. Blatter, H. Keyserling, K. P. Guito, C. K. Meschievitz, A. H. Lucas

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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 κII-A2 variable region, and HibId-2, a newly defined cross-reactive idiotype associated with a subset of anti-Hib PS antibodies having λVII 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.

Original languageEnglish (US)
Pages (from-to)788-796
Number of pages9
JournalJournal of Clinical Investigation
Volume91
Issue number3
DOIs
StatePublished - 1993

Keywords

  • antibody functional activity
  • antibody repertoire
  • cross-reactive idiotype
  • vaccine

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