Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B.
Toxins (Basel)
; 12(5)2020 05 07.
Article
em En
| MEDLINE
| ID: mdl-32392791
ABSTRACT
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Botulismo
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Clostridium botulinum
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Toxinas Botulínicas Tipo A
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Anticorpos Amplamente Neutralizantes
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Anticorpos Monoclonais
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Toxins (Basel)
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Japão