Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B
Botulinum neurotoxin (BoNT) is the most potent natural toxin known. Of the seven BoNT serotypes (A to G), types A, B, E, and F cause human botulism. Treatment of human botulism requires the development of effective toxin-neutralizing antibodies without side effects such as serum sickness and anaphyl...
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MDPI AG
2020-05-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/12/5/302 |
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| author | Takuhiro Matsumura Sho Amatsu Ryo Misaki Masahiro Yutani Anariwa Du Tomoko Kohda Kazuhito Fujiyama Kazuyoshi Ikuta Yukako Fujinaga |
| author_facet | Takuhiro Matsumura Sho Amatsu Ryo Misaki Masahiro Yutani Anariwa Du Tomoko Kohda Kazuhito Fujiyama Kazuyoshi Ikuta Yukako Fujinaga |
| author_sort | Takuhiro Matsumura |
| collection | DOAJ |
| description | Botulinum neurotoxin (BoNT) is the most potent natural toxin known. Of the seven BoNT serotypes (A to G), types A, B, E, and F cause human botulism. Treatment of human botulism requires the development of effective toxin-neutralizing antibodies without side effects such as serum sickness and anaphylaxis. In this study, we generated fully human monoclonal antibodies (HuMAbs) against serotype B BoNT (BoNT/B1) using a murine–human chimera fusion partner cell line named SPYMEG. Of these HuMAbs, M2, which specifically binds to the light chain of BoNT/B1, showed neutralization activity in a mouse bioassay (approximately 10 i.p. LD<sub>50</sub>/100 µg of antibody), and M4, which binds to the C-terminal of heavy chain, showed partial protection. The combination of two HuMAbs, M2 (1.25 µg) and M4 (1.25 µg), was able to completely neutralize BoNT/B1 (80 i.p. LD<sub>50</sub>) with a potency greater than 80 i.p. LD<sub>50</sub>/2.5 µg of antibodies, and was effective both prophylactically and therapeutically in the mouse model of botulism. Moreover, this combination showed broad neutralization activity against three type B subtypes, namely BoNT/B1, BoNT/B2, and BoNT/B6. These data demonstrate that the combination of M2 and M4 is promising in terms of a foundation for new human therapeutics for BoNT/B intoxication. |
| first_indexed | 2024-03-10T19:59:33Z |
| format | Article |
| id | doaj.art-90ba26ceb70d4313a0e0fdf0730c4938 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T19:59:33Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-90ba26ceb70d4313a0e0fdf0730c49382023-11-19T23:41:42ZengMDPI AGToxins2072-66512020-05-0112530210.3390/toxins12050302Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype BTakuhiro Matsumura0Sho Amatsu1Ryo Misaki2Masahiro Yutani3Anariwa Du4Tomoko Kohda5Kazuhito Fujiyama6Kazuyoshi Ikuta7Yukako Fujinaga8Department of Bacteriology, Graduate School of Medical Sciences, Kanazawa University, Takara-machi, Kanazawa, Ishikawa 920-8640, JapanDepartment of Bacteriology, Graduate School of Medical Sciences, Kanazawa University, Takara-machi, Kanazawa, Ishikawa 920-8640, JapanApplied Microbiology Laboratory, International Center for Biotechnology, Osaka University, Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Bacteriology, Graduate School of Medical Sciences, Kanazawa University, Takara-machi, Kanazawa, Ishikawa 920-8640, JapanDepartment of Virology, Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Veterinary Sciences, School of Life and Environmental Sciences, Osaka Prefecture University, Rinkuouraikita, Izumisano, Osaka 598-8531, JapanApplied Microbiology Laboratory, International Center for Biotechnology, Osaka University, Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Virology, Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Bacteriology, Graduate School of Medical Sciences, Kanazawa University, Takara-machi, Kanazawa, Ishikawa 920-8640, JapanBotulinum neurotoxin (BoNT) is the most potent natural toxin known. Of the seven BoNT serotypes (A to G), types A, B, E, and F cause human botulism. Treatment of human botulism requires the development of effective toxin-neutralizing antibodies without side effects such as serum sickness and anaphylaxis. In this study, we generated fully human monoclonal antibodies (HuMAbs) against serotype B BoNT (BoNT/B1) using a murine–human chimera fusion partner cell line named SPYMEG. Of these HuMAbs, M2, which specifically binds to the light chain of BoNT/B1, showed neutralization activity in a mouse bioassay (approximately 10 i.p. LD<sub>50</sub>/100 µg of antibody), and M4, which binds to the C-terminal of heavy chain, showed partial protection. The combination of two HuMAbs, M2 (1.25 µg) and M4 (1.25 µg), was able to completely neutralize BoNT/B1 (80 i.p. LD<sub>50</sub>) with a potency greater than 80 i.p. LD<sub>50</sub>/2.5 µg of antibodies, and was effective both prophylactically and therapeutically in the mouse model of botulism. Moreover, this combination showed broad neutralization activity against three type B subtypes, namely BoNT/B1, BoNT/B2, and BoNT/B6. These data demonstrate that the combination of M2 and M4 is promising in terms of a foundation for new human therapeutics for BoNT/B intoxication.https://www.mdpi.com/2072-6651/12/5/302<i>Clostridium botulinum</i>neurotoxinbotulismfully human monoclonal antibodySPYMEGtherapeutic effect |
| spellingShingle | Takuhiro Matsumura Sho Amatsu Ryo Misaki Masahiro Yutani Anariwa Du Tomoko Kohda Kazuhito Fujiyama Kazuyoshi Ikuta Yukako Fujinaga Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B Toxins <i>Clostridium botulinum</i> neurotoxin botulism fully human monoclonal antibody SPYMEG therapeutic effect |
| title | Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B |
| title_full | Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B |
| title_fullStr | Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B |
| title_full_unstemmed | Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B |
| title_short | Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B |
| title_sort | fully human monoclonal antibodies effectively neutralizing botulinum neurotoxin serotype b |
| topic | <i>Clostridium botulinum</i> neurotoxin botulism fully human monoclonal antibody SPYMEG therapeutic effect |
| url | https://www.mdpi.com/2072-6651/12/5/302 |
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