Immunogenicity and immunoprotection of the functional TL-HN fragment derived from tetanus toxin.

Autor: Liu XY; Pharmaceutical College, Henan University, Kaifeng 475001, China; Beijing Institute of Biotechnology, Beijing 100071, China., Wei DK; Pharmaceutical College, Henan University, Kaifeng 475001, China; Beijing Institute of Biotechnology, Beijing 100071, China., Li ZY; Pharmaceutical College, Henan University, Kaifeng 475001, China; Beijing Institute of Biotechnology, Beijing 100071, China., Lu JS; Beijing Institute of Biotechnology, Beijing 100071, China., Xie XM; Pharmaceutical College, Henan University, Kaifeng 475001, China. Electronic address: xxm@vip.henu.edu.cn., Yu YZ; Beijing Institute of Biotechnology, Beijing 100071, China. Electronic address: yunzhouyu@163.com., Pang XB; Pharmaceutical College, Henan University, Kaifeng 475001, China. Electronic address: pxb0411@163.com.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2023 Nov 02; Vol. 41 (46), pp. 6834-6841. Date of Electronic Publication: 2023 Oct 08.
DOI: 10.1016/j.vaccine.2023.09.032
Abstrakt: Tetanus toxin (TeNT) is a protein toxin produced by Clostridium tetani bacteria, which causes hyperreflexia and rhabdomyolysis by spastic paralysis. Like botulinum neurotoxin, TeNT comprises a heavy chain (HC) and a light chain (LC) linked via an interchain disulfide bond, which include the following three functional domains: a receptor-binding domain (Hc), a translocation domain (HN), and a catalytic domain (LC). Herein, we produced and characterized three functional domains of TeNT and three types of TeNT-derived L-HN fragments (TL-HN, TL-GS-HN and TL-2A-HN), which contained L and HN domains but lacked the Hc domain. The immunological effects of these different functional domains or fragments of TeNT were explored in an animal model. Our investigations showed the TL-HN functional fragment provided the best immunoprotection among all the TeNT functional domains. The TL-HN fragment, as a protective antigen, induced the highest levels of neutralizing antibodies, indicating that it might contain some crucial epitopes. Further experiments revealed that the protective effect of TL-HN was superior to that of the THc, TL, or THN fragments, either individually or in combination. Therefore, the TL-HN fragment exerts an important function in immune protection against tetanus toxin, providing a good basis for the development of TeNT vaccines or antibodies, and could serve as a promising subunit vaccine to replace THc or tetanus toxoid (TT).
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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