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功能性 EL-HN 片段作为预防肉毒梭菌神经毒素血清型 E 的有效候选疫苗。

Functional EL-HN Fragment as a Potent Candidate Vaccine for the Prevention of Botulinum Neurotoxin Serotype E.

机构信息

Beijing Institute of Biotechnology, Beijing 100071, China.

Institute of Life Science and Biotechnology, Beijing Jiaotong University, Beijing 100044, China.

出版信息

Toxins (Basel). 2022 Feb 11;14(2):135. doi: 10.3390/toxins14020135.

DOI:10.3390/toxins14020135
PMID:35202162
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8880310/
Abstract

produces botulinum neurotoxin (BoNT), which is the most toxic known protein and the causative agent of human botulism. BoNTs have similar structures and functions, comprising three functional domains: catalytic domain (L), translocation domain (HN), and receptor-binding domain (Hc). In the present study, BoNT/E was selected as a model toxin to further explore the immunological significance of each domain. The EL-HN fragment (L and HN domains of BoNT/E) retained the enzymatic activity without in vivo neurotoxicity. Extensive investigations showed EL-HN functional fragment had the highest protective efficacy and contained some functional neutralizing epitopes. Further experiments demonstrated the EL-HN provided a superior protective effect compared with the EHc or EHc and EL-HN combination. Thus, the EL-HN played an important role in immune protection against BoNT/E and could provide an excellent platform for the design of botulinum vaccines and neutralizing antibodies. The EL-HN has the potential to replace EHc or toxoid as the optimal immunogen for the botulinum vaccine.

摘要

产生肉毒神经毒素（BoNT），它是已知毒性最强的蛋白质，也是人类肉毒中毒的病原体。BoNTs 具有相似的结构和功能，包括三个功能域：催化域（L）、易位域（HN）和受体结合域（Hc）。在本研究中，BoNT/E 被选为模型毒素，以进一步探讨每个结构域的免疫学意义。EL-HN 片段（BoNT/E 的 L 和 HN 结构域）保留了酶活性而没有体内神经毒性。广泛的研究表明，EL-HN 功能片段具有最高的保护效力，并包含一些功能性中和表位。进一步的实验表明，与 EHc 或 EHc 和 EL-HN 联合相比，EL-HN 提供了更好的保护效果。因此，EL-HN 在针对 BoNT/E 的免疫保护中发挥了重要作用，并为肉毒杆菌疫苗和中和抗体的设计提供了一个极好的平台。EL-HN 有可能取代 EHc 或类毒素作为肉毒杆菌疫苗的最佳免疫原。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/2251c69b6c67/toxins-14-00135-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/c1b7a056eef2/toxins-14-00135-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/33358407f118/toxins-14-00135-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/63087d40d80f/toxins-14-00135-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/b08bd420a78c/toxins-14-00135-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/63c23331e4b1/toxins-14-00135-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/2251c69b6c67/toxins-14-00135-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/c1b7a056eef2/toxins-14-00135-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/33358407f118/toxins-14-00135-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/63087d40d80f/toxins-14-00135-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/b08bd420a78c/toxins-14-00135-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/63c23331e4b1/toxins-14-00135-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ca/8880310/2251c69b6c67/toxins-14-00135-g006.jpg

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