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

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 2x LD50 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.

Automated summary

The study identified monoclonal antibodies derived from memory B cells of a healthy adult immunized with the C-terminal domain of tetanus neurotoxin (TeNT). Some of these antibodies showed protective effects in mice challenged with TeNT, while others significantly prolonged survival time. The antibodies recognized distinct epitopes on tetanus toxoid, with varying binding affinities, offering promising therapeutic candidates for tetanus.