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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\u2013human 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 \u00b5g of antibody), and M4, which binds to the C-terminal of heavy chain, showed partial protection. The combination of two HuMAbs, M2 (1.25 \u00b5g) and M4 (1.25 \u00b5g), was able to completely neutralize BoNT\/B1 (80 i.p. LD50) with a potency greater than 80 i.p. LD50\/2.5 \u00b5g 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.<\/jats:p>","DOI":"10.3390\/toxins12050302","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T03:45:20Z","timestamp":1588909520000},"page":"302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Fully Human Monoclonal Antibodies Effectively Neutralizing Botulinum Neurotoxin Serotype B"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3747-829X","authenticated-orcid":false,"given":"Takuhiro","family":"Matsumura","sequence":"first","affiliation":[{"name":"Department of Bacteriology, Graduate School of Medical Sciences, Kanazawa University, Takara-machi, Kanazawa, Ishikawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0692-264X","authenticated-orcid":false,"given":"Sho","family":"Amatsu","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Graduate School of Medical Sciences, Kanazawa University, Takara-machi, Kanazawa, Ishikawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3910-8281","authenticated-orcid":false,"given":"Ryo","family":"Misaki","sequence":"additional","affiliation":[{"name":"Applied Microbiology Laboratory, International Center for Biotechnology, Osaka University, Yamadaoka, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Yutani","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Graduate School of Medical Sciences, Kanazawa University, Takara-machi, Kanazawa, Ishikawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anariwa","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Virology, Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Kohda","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, School of Life and Environmental Sciences, Osaka Prefecture University, Rinkuouraikita, Izumisano, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhito","family":"Fujiyama","sequence":"additional","affiliation":[{"name":"Applied Microbiology Laboratory, International Center for Biotechnology, Osaka University, Yamadaoka, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Ikuta","sequence":"additional","affiliation":[{"name":"Department of Virology, Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita, Osaka 565-0871, Japan"},{"name":"The Japan Science and Technology Agency\/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, Tokyo 102-0076, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukako","family":"Fujinaga","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Graduate School of Medical Sciences, Kanazawa University, Takara-machi, Kanazawa, Ishikawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1152\/physrev.2000.80.2.717","article-title":"Neurotoxins affecting neuroexocytosis","volume":"80","author":"Schiavo","year":"2000","journal-title":"Physiol. 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