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In addition to the critical protective antigen found in the full BoNT molecule, the receptor binding domain (Hc domain), BoNTs also harbour another essential protective antigen\u2014the light chain\u2010translocation domain (L\u2010HN domain). Leveraging these pivotal protective antigens, we genetically engineered a series of inactivated chimeric molecules incorporating L\u2010HN and Hc domains of BoNT\/A and E. The structure of these chimeric molecules, mirror BoNT\/A and E, but are devoid of enzyme activity. Experimental findings demonstrated that a lead candidate mEL\u2010HN\u2010mAHc harnessing the inactivated protease LCHN\/E with the mutated gangliosides binding site Hc\/A (mE\u2010mA) elicited robust immune protection against BoNT\/A and E simultaneously in a mouse model, requiring low immune dosages and minimal immunisations. Moreover, mE\u2010mA exhibited high protective efficacy against BoNT\/A and E in guinea pigs and New Zealand white rabbits, resulting in elevated neutralising antibody titres. Furthermore, mE\u2010mA proved to be a more stable and safer vaccine compared to formaldehyde\u2010inactivated toxoid. Our data underscore the genetically engineered mE\u2010mA as a highly effective bivalent vaccine against BoNT\/A and E, paving the way for the development of polyvalent vaccines against biotoxins.<\/jats:p>","DOI":"10.1111\/imm.13867","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T06:19:03Z","timestamp":1727849943000},"page":"113-127","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["New Engineered\u2010Chimeric Botulinum Neurotoxin Mutant Acts as an Effective Bivalent Vaccine Against Botulinum Neurotoxin Serotype A and E"],"prefix":"10.1111","volume":"174","author":[{"given":"Jingrong","family":"Wang","sequence":"first","affiliation":[{"name":"Laboratory of Advanced Biotechnology Beijing Institute of Biotechnology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiansheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Laboratory 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