pubmed-article:12183544 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:12183544 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
pubmed-article:12183544 | lifeskim:mentions | umls-concept:C0305065 | lld:lifeskim |
pubmed-article:12183544 | lifeskim:mentions | umls-concept:C0025936 | lld:lifeskim |
pubmed-article:12183544 | lifeskim:mentions | umls-concept:C0439849 | lld:lifeskim |
pubmed-article:12183544 | lifeskim:mentions | umls-concept:C0032594 | lld:lifeskim |
pubmed-article:12183544 | lifeskim:mentions | umls-concept:C1708726 | lld:lifeskim |
pubmed-article:12183544 | lifeskim:mentions | umls-concept:C0003241 | lld:lifeskim |
pubmed-article:12183544 | lifeskim:mentions | umls-concept:C0205151 | lld:lifeskim |
pubmed-article:12183544 | lifeskim:mentions | umls-concept:C0358321 | lld:lifeskim |
pubmed-article:12183544 | pubmed:issue | 9 | lld:pubmed |
pubmed-article:12183544 | pubmed:dateCreated | 2002-8-16 | lld:pubmed |
pubmed-article:12183544 | pubmed:abstractText | To investigate the influence of antibody structure and specificity on antibody efficacy against Streptococcus pneumoniae, human monospecific antibodies (MAbs) to serotype 3 pneumococcal capsular polysaccharide (PPS-3) were generated from transgenic mice reconstituted with human immunoglobulin loci (XenoMouse mice) vaccinated with a PPS-3-tetanus toxoid conjugate and their molecular genetic structures, epitope specificities, and protective efficacies in normal and complement-deficient mice were determined. Nucleic acid sequence analysis of three MAbs (A7, 1A2, and 7C5) revealed that they use two different V(H)3 genes (A7 and 1A2 both use V3-15) and three different V(kappa) gene segments. The MAbs were found to have similar affinities for PPS-3 but different epitope specificities and CDR3 regions. Both A7 and 7C5 had a lysine at the V(H)-D junction, whereas 1A2 had a threonine. Challenge experiments with serotype 3 S. pneumoniae in BALB/c mice revealed that both 10- and 1- micro g doses of A7 and 7C5 were protective, while only a 10- micro g dose of 1A2 was protective. Both A7 and 7C5 were also protective in mice lacking either an intact alternative (FB(-/-)) or classical (C4(-/-)) complement pathway, but 1A2 was not protective in either strain. Our data suggest that PPS-3 consists of epitopes that can elicit both highly protective and less protective antibodies and that the superior efficacies of certain antibodies may be a function of their structures and/or specificities. Further investigation of relationships between structure, specificity, and efficacy for defined MAbs to PPS may identify antibody features that might be useful surrogates for antibody (and vaccine) efficacy. | lld:pubmed |
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pubmed-article:12183544 | pubmed:language | eng | lld:pubmed |
pubmed-article:12183544 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12183544 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:12183544 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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pubmed-article:12183544 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:12183544 | pubmed:month | Sep | lld:pubmed |
pubmed-article:12183544 | pubmed:issn | 0019-9567 | lld:pubmed |
pubmed-article:12183544 | pubmed:author | pubmed-author:LeesAA | lld:pubmed |
pubmed-article:12183544 | pubmed:author | pubmed-author:ZhongZZ | lld:pubmed |
pubmed-article:12183544 | pubmed:author | pubmed-author:ChangQQ | lld:pubmed |
pubmed-article:12183544 | pubmed:author | pubmed-author:PirofskiLL | lld:pubmed |
pubmed-article:12183544 | pubmed:author | pubmed-author:PeknaMM | lld:pubmed |
pubmed-article:12183544 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:12183544 | pubmed:volume | 70 | lld:pubmed |
pubmed-article:12183544 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:12183544 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:12183544 | pubmed:pagination | 4977-86 | lld:pubmed |
pubmed-article:12183544 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |