title: Immunogenetic analysis of the immune response to pneumococcal polysaccharide.
abstract: Pneumococcal serotype-specific anti-capsular polysaccharide antibodies protect against invasive pneumococcal disease. Within an individual the diversity of these antibodies is limited. To evaluate the repertoire of antibodies to pneumococcus and determine whether oligoclonality is seen both between serotypes and between individuals, we sampled the B cell repertoire induced by polysaccharide and conjugate vaccine in adult volunteers. Fifteen hybridomas secreting pneumococcus-specific monoclonal antibodies were generated from five volunteers. Ten were isotype switched, six were IgG2 and four were IgA. These included two isotype switch variants of the same clone. V(H)3 and V(kappa)2 were used by 10/15 and 7/13 of the sequenced clones, respectively, with identical genes, V(H)3-48 and V(kappa)2-A17 used by a number of volunteers to a variety of serotypes. VDJ junctional characteristics and complementarity-determining region (CDR) 3 length were variable. High levels of somatic mutation in CDR1 and 2, inconsistent with a primary response, were found in 10/11 of the isotype-switched antibodies, including those induced by plain polysaccharide antigens. These data suggest that wild-type infection or nasopharyngeal carriage of Streptococcus pneumoniae in adults may induce memory and the response to subsequent immunization with plain polysaccharide or conjugate pneumococcal vaccines may have the characteristics of a secondary response.
authors.affiliation: Immunobiology Unit, Institute of Child Health, University College London, London, GB.
authors.forename: H E
authors.initials: HE
authors.lastname: Baxendale
authors.forename: Z
authors.initials: Z
authors.lastname: Davis
authors.forename: H N
authors.initials: HN
authors.lastname: White
authors.forename: M B
authors.initials: MB
authors.lastname: Spellerberg
authors.forename: F K
authors.initials: FK
authors.lastname: Stevenson
authors.forename: D
authors.initials: D
authors.lastname: Goldblatt
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D000915:Antibody Affinity; D000916:Antibody Diversity / Q000235:genetics* / Q000276:immunology*; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001428:Bacterial Vaccines / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D005803:Genes, Immunoglobulin / Q000235:genetics*; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D007132:Immunoglobulin Isotypes / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D022401:Meningococcal Vaccines; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D016415:Sequence Alignment; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007132:Immunoglobulin Isotypes; D007135:Immunoglobulin Variable Region; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate