Journal of Microbiology and Biotechnology

  • 제28권12호
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  • Pages.2113-2120
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  • 2018
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  • 1017-7825(pISSN)
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  • 1738-8872(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
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Generation of a Human Monoclonal Antibody to Cross-Reactive Material 197 (CRM197) and Development of a Sandwich ELISA for CRM197 Conjugate Vaccines

  • Kim, Dain (Department of Systems Immunology, College of Biomedical Science, Kangwon National University) ;
  • Yoon, Hyeseon (Eubiologics Co., Ltd.) ;
  • Kim, Sangkyu (Department of Systems Immunology, College of Biomedical Science, Kangwon National University) ;
  • Wi, Jimin (Scripps Korea Antibody Institute) ;
  • Chae, Heesu (Department of Systems Immunology, College of Biomedical Science, Kangwon National University) ;
  • Jo, Gyunghee (Department of Systems Immunology, College of Biomedical Science, Kangwon National University) ;
  • Yoon, Jun-Yeol (Department of Systems Immunology, College of Biomedical Science, Kangwon National University) ;
  • Kim, Heeyoun (Eubiologics Co., Ltd.) ;
  • Lee, Chankyu (Eubiologics Co., Ltd.) ;
  • Kim, Se-Ho (Department of Systems Immunology, College of Biomedical Science, Kangwon National University) ;
  • Hong, Hyo Jeong (Department of Systems Immunology, College of Biomedical Science, Kangwon National University)
  • 투고 : 2018.10.04
  • 심사 : 2018.10.18
  • 발행 : 2018.12.28
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초록

Cross-reactive material 197 ($CRM_{197}$) is a non-toxic mutant of diphtheria toxin containing a single amino acid substitution of glycine 52 with glutamic acid. $CRM_{197}$ has been used as a carrier protein for poorly immunogenic polysaccharide antigens to improve immune responses. In this study, to develop a sandwich ELISA that can detect $CRM_{197}$ and $CRM_{197}$ conjugate vaccines, we generated a human anti-$CRM_{197}$ monoclonal antibody (mAb) 3F9 using a phage-displayed human synthetic Fab library and produced mouse anti-$CRM_{197}$ polyclonal antibody. The affinity ($K_D$) of 3F9 for $CRM_{197}$ was 3.55 nM, based on Bio-Layer interferometry, and it bound specifically to the B fragment of $CRM_{197}$. The sandwich ELISA was carried out using 3F9 as a capture antibody and the mouse polyclonal antibody as a detection antibody. The detection limit of the sandwich ELISA was <1 ng/ml $CRM_{197}$. In addition, the 3F9 antibody bound to the $CRM_{197}$-polysaccharide conjugates tested in a dose-dependent manner. This ELISA system will be useful for the quantification and characterization of $CRM_{197}$ and $CRM_{197}$ conjugate vaccines. To our knowledge, this study is the first to generate a human monoclonal antibody against $CRM_{197}$ and to develop a sandwich ELISA for $CRM_{197}$ conjugate vaccines.

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피인용 문헌

  1. Epitope Mapping of the Diphtheria Toxin and Development of an ELISA-Specific Diagnostic Assay vol.9, pp.4, 2018, https://doi.org/10.3390/vaccines9040313
  2. Cross-reaction between mouse and rat immunoglobulin G: does it matter in sandwich ELISA? vol.19, pp.1, 2018, https://doi.org/10.1186/s43141-021-00222-2