{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:46:29Z","timestamp":1780433189280,"version":"3.54.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Botulinum neurotoxin (BoNT), produced by <jats:italic>Clostridium botulinum<\/jats:italic>, is the most toxic protein known, capable of causing severe paralysis and posing a significant bioterrorism threat due to its extreme lethality even in minute quantities. Despite this, there are currently no FDA-approved vaccines for widespread public use. To address this urgent need, we have developed an innovative vaccine platform by fusing the neuronal binding domain of BoNT\/E (Hc\/E) with core-streptavidin (CS), resulting in a stable CS-Hc\/E vaccine. Mice vaccinated with CS-Hc\/E exhibited superior antibody titers compared to those receiving Hc\/E alone. To develop a trivalent vaccine against BoNT\/A, BoNT\/B, and BoNT\/E\u2014 key contributors to the vast majority of human botulism\u2014we conjugated CS-Hc\/E with a biotinylated atoxic chimeric protein incorporating neutralizing epitopes from BoNT\/A and BoNT\/B. This chimeric protein includes the binding domain of BoNT\/A, along with the protease-inactive light chain and translocation domains of BoNT\/B. The interaction between CS and biotin formed a stable tetrameric antigen, EBA. Vaccination with EBA in mice elicited robust antibody responses and provided complete protection against lethal doses of BoNT\/A, BoNT\/B, and BoNT\/E. Our findings highlight EBA\u2019s potential as a stable and effective broad-spectrum vaccine against BoNT. Moreover, our technology offers a versatile platform for developing multivalent, stable vaccines targeting various biological threats by substituting the BoNT domain(s) with neutralizing epitopes from other life-threatening pathogens, thereby enhancing public health preparedness and biodefense strategies.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1469919","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T04:37:40Z","timestamp":1725856660000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel platform for engineering stable and effective vaccines against botulinum neurotoxins A, B and 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