Immunogenetic analysis of the immune response to pneumococcal polysaccharide

HE Baxendale, Z Davis, HN White… - European journal of …, 2000 - Wiley Online Library
HE Baxendale, Z Davis, HN White, MB Spellerberg, FK Stevenson, D Goldblatt
European journal of immunology, 2000Wiley Online Library
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 …
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. VH3 and Vκ2 were used by 10 / 15 and 7 / 13 of the sequenced clones, respectively, with identical genes, VH3 – 48 and Vκ2‐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.
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