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Four clones (2\u20134, 2\u20135, 9\u20134 and B1) were selected for chimerization on the basis of their neutralizing activity against BoNT\/A and the cDNA of the variable regions of their heavy (V<jats:sub>H<\/jats:sub>) and light chains (V<jats:sub>L<\/jats:sub>) were fused with the upstream regions of the constant counterparts of human kappa light and gamma 1 heavy chain genes, respectively. CHO\u2010DG44 cells were transfected with these plasmids and mouse\u2010human chimeric antibodies (AC24, AC25, AC94 and ACB1) purified to examine their binding and neutralizing activities. Each chimeric antibody exhibited almost the same capability as each parent mouse mAb to bind and neutralize activities against BoNT\/A. From the chimeric antibodies against BoNT\/A, shuffling chimeric antibodies designed with replacement of their V<jats:sub>H<\/jats:sub>or V<jats:sub>L<\/jats:sub>domains were constructed. A shuffling antibody (AC2494) that derived its V<jats:sub>H<\/jats:sub>and V<jats:sub>L<\/jats:sub>domains from chimeric antibodies AC24 and AC94, respectively, showed much higher neutralizing activity than did other shuffling antibodies and parent counterparts. This result indicates that it is possible to build high\u2010potency neutralizing chimeric antibodies by selecting and shuffling V<jats:sub>H<\/jats:sub>and V<jats:sub>L<\/jats:sub>domains from a variety of repertoires. A shuffling chimeric antibody might be the best candidate for replacing horse antitoxin for inducing passive immunotherapy against botulism.<\/jats:p>","DOI":"10.1111\/j.1348-0421.2012.00503.x","type":"journal-article","created":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T18:25:11Z","timestamp":1346523911000},"page":"748-755","source":"Crossref","is-referenced-by-count":3,"title":["Characterization of neutralizing mouse\u2010human chimeric and shuffling antibodies against botulinum neurotoxin 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