Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China; Trinomab Biotech Co., Ltd, Zhuhai 519040, China.
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
Cell Rep. 2021 May 4;35(5):109070. doi: 10.1016/j.celrep.2021.109070.
Four potent native human monoclonal antibodies (mAbs) targeting distinct epitopes on tetanus toxin (TeNT) are isolated with neutralization potency ranging from approximately 17 mg to 6 mg each that are equivalent to 250 IU of human anti-TeNT immunoglobulin. TT0170 binds fragment B, and TT0069 and TT0155 bind fragment AB. mAb TT0067 binds fragment C and blocks the binding of TeNT to gangliosides. The co-crystal structure of TT0067 with fragment C of TeNT at a 2.0-Å resolution demonstrates that mAb TT0067 directly occupies the W pocket of one of the receptor binding sites on TeNT, resulting in blocking the binding of TeNT to ganglioside on the surface of host cells. This study reveals at the atomic level the mechanism of action by the TeNT neutralizing antibody. The key neutralization epitope on the fragment C of TeNT identified in our work provides the critical information for the development of fragment C of TeNT as a better and safer tetanus vaccine.
四种强效的人源单克隆抗体（mAb）针对破伤风毒素（TeNT）的不同表位，中和效力约为每 17mg 到 6mg，相当于 250IU 的人抗 TeNT 免疫球蛋白。TT0170 结合片段 B，TT0069 和 TT0155 结合片段 AB。mAb TT0067 结合片段 C 并阻断 TeNT 与神经节苷脂的结合。TT0067 与 TeNT 片段 C 的 2.0-Å 分辨率共晶结构表明，mAb TT0067 直接占据 TeNT 上一个受体结合位点的 W 口袋，从而阻止 TeNT 与宿主细胞表面神经节苷脂的结合。这项研究在原子水平上揭示了 TeNT 中和抗体的作用机制。我们的工作中确定的 TeNT 片段 C 上的关键中和表位为 TeNT 片段 C 作为一种更好、更安全的破伤风疫苗的开发提供了关键信息。
