Tetanus vaccine-induced human neutralizing antibodies provide full protection against neurotoxin challenge in mice.

Autor: Zhang G; Beijing Institute of Biotechnology, Beijing 100071, China., Yu R; Beijing Institute of Biotechnology, Beijing 100071, China., Chi X; Beijing Institute of Biotechnology, Beijing 100071, China., Chen Z; Beijing Institute of Biotechnology, Beijing 100071, China., Hao M; Beijing Institute of Biotechnology, Beijing 100071, China., Du P; Beijing Institute of Biotechnology, Beijing 100071, China., Fan P; Beijing Institute of Biotechnology, Beijing 100071, China., Liu Y; Beijing Institute of Biotechnology, Beijing 100071, China., Dong Y; Beijing Institute of Biotechnology, Beijing 100071, China., Fang T; Beijing Institute of Biotechnology, Beijing 100071, China., Chen Y; Beijing Institute of Biotechnology, Beijing 100071, China., Song X; Beijing Institute of Biotechnology, Beijing 100071, China., Liu S; Beijing Institute of Biotechnology, Beijing 100071, China., Li J; Beijing Institute of Biotechnology, Beijing 100071, China., Yu C; Beijing Institute of Biotechnology, Beijing 100071, China., Chen W; Beijing Institute of Biotechnology, Beijing 100071, China. Electronic address: cw0226@foxmail.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2021 Feb; Vol. 91, pp. 107297. Date of Electronic Publication: 2020 Dec 21.
DOI: 10.1016/j.intimp.2020.107297
Abstrakt: Clostridium tetani causes life-threatening disease by producing tetanus neurotoxin (TeNT), one of the most toxic protein substances. Toxicosis can be prevented and cured by administration of anti-TeNT neutralizing antibodies. Here, we identified a series of monoclonal antibodies (mAbs) derived from memory B cells of a healthy adult immunized with the C-terminal domain of TeNT (TeNT-Hc). Thirteen mAbs bound to both tetanus toxoid (TT) and TeNT-Hc, while two mAbs recognized only TT. VH3-23 was the most frequently used germline gene in these TT-binding mAbs, and the pairwise identity values of the VH gene sequences ranged from 27% to 69%. Three of these mAbs-T3, T7, and T9-6-completely protected mice from challenge with 2× LD 50 of TeNT, and two (T2 and T18) significantly prolonged the survival time. The five neutralizing mAbs recognized distinct epitopes on TT, with binding affinities ranging from 0.123 to 11.9 nM. Our study provides promising therapeutic candidates for tetanus.
(Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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