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Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B

1
Department of Bacteriology, Graduate School of Medical Sciences, Kanazawa University, Takara-machi, Kanazawa, Ishikawa 920-8640, Japan
2
Applied Microbiology Laboratory, International Center for Biotechnology, Osaka University, Yamadaoka, Suita, Osaka 565-0871, Japan
3
Department of Virology, Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita, Osaka 565-0871, Japan
4
Department of Veterinary Sciences, School of Life and Environmental Sciences, Osaka Prefecture University, Rinkuouraikita, Izumisano, Osaka 598-8531, Japan
5
The Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Tokyo 102-0076, Japan
*
Author to whom correspondence should be addressed.
Toxins 2020, 12(5), 302; https://doi.org/10.3390/toxins12050302
Received: 26 March 2020 / Revised: 3 May 2020 / Accepted: 4 May 2020 / Published: 7 May 2020
(This article belongs to the Section Bacterial Toxins)
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. LD50/100 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. LD50) with a potency greater than 80 i.p. LD50/2.5 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. View Full-Text
Keywords: Clostridium botulinum; neurotoxin; botulism; fully human monoclonal antibody; SPYMEG; therapeutic effect; preventive effect Clostridium botulinum; neurotoxin; botulism; fully human monoclonal antibody; SPYMEG; therapeutic effect; preventive effect
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MDPI and ACS Style

Matsumura, T.; Amatsu, S.; Misaki, R.; Yutani, M.; Du, A.; Kohda, T.; Fujiyama, K.; Ikuta, K.; Fujinaga, Y. Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B. Toxins 2020, 12, 302. https://doi.org/10.3390/toxins12050302

AMA Style

Matsumura T, Amatsu S, Misaki R, Yutani M, Du A, Kohda T, Fujiyama K, Ikuta K, Fujinaga Y. Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B. Toxins. 2020; 12(5):302. https://doi.org/10.3390/toxins12050302

Chicago/Turabian Style

Matsumura, Takuhiro, Sho Amatsu, Ryo Misaki, Masahiro Yutani, Anariwa Du, Tomoko Kohda, Kazuhito Fujiyama, Kazuyoshi Ikuta, and Yukako Fujinaga. 2020. "Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B" Toxins 12, no. 5: 302. https://doi.org/10.3390/toxins12050302

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