title: Age-dependent V region expression in the human antibody response to the Haemophilus influenzae type b polysaccharide.
abstract: The human L chain antibody repertoire specific for the Haemophilus influenzae type b (Hib) polysaccharide (PS) is composed of kappa I, kappa II, kappa III, kappa IV, and lambda L chain V regions, but the most commonly occurring VL is encoded by the unmutated V kappa II-A2 gene. To determine whether this VL repertoire is influenced by age, we used idiotypic probes to monitor V kappa II-A2, V lambda, and V kappa III usage in the antibody response to an Hib PS-protein conjugate vaccine. A single dose of a vaccine consisting of Hib PS coupled to an outer membrane protein complex of Neisseria meningitidis was administered. Adults (n = 35), 18-month-old infants (n = 35), and 2-month-old infants (n = 46), all with > or = 0.9 microgram/ml anti-Hib PS antibodies, were tested for VL region markers in postvaccination sera. V kappa III anti-Hib PS antibodies were not detected in any of the 2-month-old infants but were detected in 29% of the 18-month-old infants and 69% of the adults (p < 0.001). The lack of kappa III antibodies in 2-month-old infants could not be accounted for by lack of a kappa response, because kappa antibodies to Hib PS were present (> 0.15 microgram/ml) in 45% of these infants. Hibld-1, an idiotope expressed by anti-Hib PS antibodies having the kappa II-A2 V region, was present in postvaccination sera of 66% of the adults and 80% of the 18-month-old infants but was less frequent in the 2-month-old infants (35%, p < 0.001). In contrast, Hibld-2, which is an idiotope expressed by a subset of V lambda VII anti-Hib PS antibodies, was rare or infrequent in adults and 18-month-old infants (0% and 6%, respectively) but was present in 43% of 2-month-old infants (p < 0.001). Our findings demonstrate that dramatic changes in VL region utilization occur in the human antibody response to this Hib PS conjugate vaccine as a function of age. Because previous studies have shown that V region usage correlates with antibody fine specificity and avidity for Hib PS, these age-related differences in V region expression may affect the ability of vaccines to confer protective immunity at different ages.
authors.affiliation: Children's Hospital Oakland Research Institute, CA 94609.
authors.forename: A H
authors.initials: AH
authors.lastname: Lucas
authors.forename: F H
authors.initials: FH
authors.lastname: Azmi
authors.forename: C M
authors.initials: CM
authors.lastname: Mink
authors.forename: D M
authors.initials: DM
authors.lastname: Granoff
mesh_terms: D000328:Adult; D000367:Age Factors; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D016667:Bacterial Capsules; D001428:Bacterial Vaccines / Q000276:immunology*; D005260:Female; D018073:Haemophilus Vaccines; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000032:analysis; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis*; D007223:Infant; D008297:Male; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D011135:Polysaccharides, Bacterial