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BRIEF RESEARCH REPORT article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1469919

Novel platform for engineering stable and effective vaccines against botulinum neurotoxins A, B and E

Provisionally accepted
Yang Liu Yang Liu 1Xiaoyu Liu Xiaoyu Liu 2Weiwei Chen Weiwei Chen 1Yunzhou Yu Yunzhou Yu 2Jianghui Meng Jianghui Meng 3*Jiafu Wang Jiafu Wang 3
  • 1 Henan University, Kaifeng, Henan Province, China
  • 2 Beijing Institute of Biotechnology, Beijing, China
  • 3 Dublin City University, Dublin, County Dublin, Ireland

The final, formatted version of the article will be published soon.

    Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, 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-key contributors to the vast majority of human botulism-we 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's 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.

    Keywords: Vaccine, Botulinum Neurotoxin, Streptavidin, Botulism, Therapeutics, Protein Engineering

    Received: 24 Jul 2024; Accepted: 26 Aug 2024.

    Copyright: © 2024 Liu, Liu, Chen, Yu, Meng and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jianghui Meng, Dublin City University, Dublin, Dublin 9, County Dublin, Ireland

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.