{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T21:57:45Z","timestamp":1783461465351,"version":"3.55.0"},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,4,4]],"date-time":"2021-04-04T00:00:00Z","timestamp":1617494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Compared to conventional antisera strategies, monoclonal antibodies (mAbs) represent an alternative and safer way to treat botulism, a fatal flaccid paralysis due to botulinum neurotoxins (BoNTs). In addition, mAbs offer the advantage to be produced in a reproducible manner. We previously identified a unique and potent mouse mAb (TA12) targeting BoNT\/A1 with high affinity and neutralizing activity. In this study, we characterized the molecular basis of TA12 neutralization by combining Hydrogen\/Deuterium eXchange Mass Spectrometry (HDX\u2010MS) with site\u2010directed mutagenesis and functional studies. We found that TA12 recognizes a conformational epitope located at the interface between the H\n                    <jats:sub>CN<\/jats:sub>\n                    and H\n                    <jats:sub>CC<\/jats:sub>\n                    subdomains of the BoNT\/A1 receptor\u2010binding domain (H\n                    <jats:sub>C<\/jats:sub>\n                    ). The TA12\u2010binding interface shares common structural features with the ciA\u2010C2 VHH epitope and lies on the face opposite recognized by ciA\u2010C2\u2010 and the CR1\/CR2\u2010neutralizing mAbs. The single substitution of N1006 was sufficient to affect TA12 binding to H\n                    <jats:sub>C<\/jats:sub>\n                    confirming the position of the epitope. We further uncovered that the TA12 epitope overlaps with the BoNT\/A1\u2010binding site for both the neuronal cell surface receptor synaptic vesicle glycoprotein 2 isoform C (SV2C) and the GT1b ganglioside. Hence, TA12 potently blocks the entry of BoNT\/A1 into neurons by interfering simultaneously with the binding of SV2C and to a lower extent GT1b. Our study reveals the unique neutralization mechanism of TA12 and emphasizes on the potential of using single mAbs for the treatment of botulism type A.\n                  <\/jats:p>","DOI":"10.1096\/fj.202002492r","type":"journal-article","created":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T02:56:03Z","timestamp":1617591363000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Characterization of a highly neutralizing single monoclonal antibody to botulinum neurotoxin type A"],"prefix":"10.1096","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1758-8237","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Brier","sequence":"first","affiliation":[{"name":"Biological NMR Technological Platform Institut Pasteur, CNRS UMR3528 Paris 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Marechal","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Toxines Bact\u00e9riennes, UMR CNRS 2001 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9080-7761","authenticated-orcid":false,"given":"Emmanuel","family":"Lemichez","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Toxines Bact\u00e9riennes, UMR CNRS 2001 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9305-8989","authenticated-orcid":false,"given":"Michel R.","family":"Popoff","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Toxines Bact\u00e9riennes, UMR CNRS 2001 Paris 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