TY - JOUR
T1 - Variable region expression in the antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-protein conjugates
T2 - Description of a new λ light chain-associated idiotype and the relation between idiotype expression, avidity, and vaccine formulation
AU - Granoff, D. M.
AU - Shackelford, P. G.
AU - Holmes, S. J.
AU - Murphy, T. V.
AU - Osterholm, Michael T.
AU - Anderson, E. L.
AU - Belshe, R. B.
AU - Esbenshade, J.
AU - Blatter, M.
AU - Keyserling, H.
AU - Guito, K. P.
AU - Meschievitz, C. K.
AU - Lucas, A. H.
PY - 1993/3
Y1 - 1993/3
N2 - 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 crossreactive 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 Hibld-l 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.
AB - 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 crossreactive 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 Hibld-l 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.
KW - Antibody functional activity
KW - Antibody repertoire
KW - Cross-reactive idiotype
KW - Vaccine
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M3 - Article
C2 - 8450060
AN - SCOPUS:0027522632
SN - 0021-9738
VL - 91
SP - 788
EP - 796
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
ER -