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

• Published in: Vaccine 2023-11, Vol.41 (46), p.6834-6841
• Main Authors: Liu, Xu-Yang, Wei, Dong-Kui, Li, Zhi-Ying, Lu, Jian-Sheng, Xie, Xin-Mei, Yu, Yun-Zhou, Pang, Xiao-Bin
• Format: Article
• Language: English
• Subjects: active sites; Animal models; Animals; Antibodies; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Antibodies, Neutralizing - immunology; Antigens; Botulinum toxin; Chemical bonds; Clostridium tetani; Cytoplasm; disulfide bonds; domain; E coli; Epitopes; Female; Fragments; Functional domain; Immune protection; Immunization; Immunogenicity; Immunology; Laboratory animals; Mice; Mice, Inbred BALB C; Neurotoxicity; Neurotoxins; Paralysis; Peptide Fragments - immunology; Plasmids; Poisoning; Protective antigen; protective effect; Proteins; Rhabdomyolysis; Subunit vaccine; subunit vaccines; Tetanus; Tetanus - immunology; Tetanus - prevention & control; Tetanus toxin; Tetanus Toxin - immunology; TL-HN fragment; Toxins; Translocation; Vaccines
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2023.09.032

•TL-HN afforded the best immunoprotection among all the TeNT functional domains.•TL + THN combination showed no synergistic effect on protective potency against TeNT.•There are important neutralizing antibody epitopes at L and HN domains of TeNT.•TL-HN lacking the Hc domain is a good candidate subunit vaccine against TeNT. 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).