Immunogenetic analysis of the immune response to pneumococcal polysaccharide

Pneumococcal serotype-specific anti-capsular polysaccharide antibodies prot ect against invasive pneumococcal disease. Within an individual the diversi ty 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 hybri domas secreting pneumococcus-specific monoclonal antibodies were generated from five volunteers. Ten were isotype switched, six were IgG2 and four wer e 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, respecti vely, 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 co mplementarity-determining region (CDR) 3 length were variable. High levels of somatic mutation in CDR1 and 2, inconsistent with a primary response, we re found in 10/11 of the isotype-switched antibodies, including those induc ed by plain polysaccharide antigens. These data suggest that wild-type infe ction or nasopharyngeal carriage of Streptococcus pneumoniae in adults may induce memory and the response to subsequent immunization with plain polysa ccharide or conjugate pneumococcal vaccines may have the characteristics of a secondary response.