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Characterization of neutralizing mouse-human chimeric and shuffling antibodies against botulinum neurotoxin A.
MedLine Citation:
PMID:  22938032     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Mouse-human chimeric monoclonal antibodies that can neutralize botulinum neurotoxins were developed. We attempted to establish mouse hybridoma cell clones that produced monoclonal antibodies neutralizing botulinum neurotoxin serotype A (BoNT/A). Four clones (2-4, 2-5, 9-4 and B1) were selected for chimerization on the basis of neutralizing activity against BoNT/A, and cDNA of variable regions of heavy (V(H) ) and light chains (V(L) ) were fused with the upstream regions of the constant counterparts of human kappa light and gamma 1 heavy chain genes, respectively. CHO-DG44 cells were transfected with these plasmids and mouse-human chimeric antibodies (AC24, AC25, AC94 and ACB1) were purified to examine their binding and neutralizing activities. Every chimeric antibody exhibited almost the same capability to each parent mouse mAb in binding and neutralizing activities against BoNT/A. We constructed shuffling chimeric antibodies designed with replacement of V(H) or V(L) domain among chimeric antibodies against BoNT/A. A shuffling antibody (AC2494) that derived its V(H) and V(L) domains from chimeric antibodies AC24 and AC94, respectively, showed much higher neutralizing activity than other shuffling antibodies and parent counterparts. This result indicates that it is possible to build high-potency neutralizing chimeric antibodies by selecting and shuffling V(H) and V(L) domains from a variety of repertoires. A shuffling chimeric antibody might be the best candidate for passive immunotherapy for botulism in place of horse antitoxin.
Authors:
Masafumi Mukamoto; Hiroaki Maeda; Tomoko Kohda; Chikateru Nozaki; Motohide Takahashi; Shunji Kozaki
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-31
Journal Detail:
Title:  Microbiology and immunology     Volume:  -     ISSN:  1348-0421     ISO Abbreviation:  Microbiol. Immunol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-9-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7703966     Medline TA:  Microbiol Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Societies and Blackwell Publishing Asia Pty Ltd.
Affiliation:
Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku Orai-Kita, Izumisano, Osaka 598-8531, Japan KAKETSUKEN(The Chemo-Sero-Therapeutic Research Institute) Kikuchi Research Center, Kyokushi Kikuchi, Kumamoto 869-1298, Japan Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
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