التفاصيل البيبلوغرافية
| العنوان: |
Novel platform for engineering stable and effective vaccines against botulinum neurotoxins A, B and E. |
| المؤلفون: |
Yang Liu, Xiaoyu Liu, Weiwei Chen, Yunzhou Yu, Jianghui Meng, Jiafu Wang |
| المصدر: |
Frontiers in Immunology; 2024, p1-10, 10p |
| مصطلحات موضوعية: |
BOTULINUM toxin, CHIMERIC proteins, COMBINED vaccines, CLOSTRIDIUM botulinum, VACCINE effectiveness |
| مستخلص: |
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 broadspectrum 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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