Potent Neutralizing Native Human Monoclonal Antibody that Recognizes the Ganglioside Receptor-Binding Pocket of Tetanus Toxin

Abstract

Four potent native human mAbs targeting distinct epitopes on TeNT were isolated with neutralization potency ranging from approximately 17 mg to 6 mg each equivalent to 250IU of human anti-TeNT immunoglobulin. TT0170 binds fragment B, TT0069 and TT0155 bind fragment AB. MAb TT0067 binds fragment C and blocks the binding of TeNT to gangliosides, Co-crystal structure of TT0067 with fragment C of TeNT at 2.01 A resolution demonstrated 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 to neutralize TeNT, and revealed at the first time at atomic level the mechanism of action by TeNT neutralizing antibody and the key neutralization epitope on the fragment C of TeNT, and provided the critical information for development of fragment C of TeNT as a better and safer tetanus vaccine.