Enhanced In Vivo Tetanus Toxin Neutralizing Potency of an Anti‐Toxin Monoclonal Antibody Following Antibody Chimerization

Each immunoglobulin molecule consists of two functional independent regions, including variable and constant regions. Toxin neutralization by antibody is mainly mediated by the variable regions. Here, we report that constant region chimerization of a mouse anti-tetanus toxin monoclonal antibody (MAb), 1F3E3, confers enhanced in vivo toxin neutralizing activity of the chimeric MAb compared to its parental murine counterpart. A mouse-human chimeric MAb, c-1F3E3, was generated by recombinant DNA technology and its structural and functional characteristics, including affinity constant, reactivity pattern to tetanus toxin fragments, inhibiting the toxin binding to GT1b ganglioside receptors as well as in vivo toxin neutralizing activity in mice were assessed and compared with those of the murine MAb. Both the murine and chimeric MAbs displayed similar reactivity patterns as well as similar toxin binding affinity constant. The target epitope of both MAbs was located in fragment C of the toxin and both were able to inhibit binding of the toxin to GT1b ganglioside at a comparable level. While 1F3E3 MAb failed to neutralize the toxin in vivo, the chimeric MAb (c-1F3E3) showed a strong and dose-dependent toxin neutralizing potency leading to improved protection and survival in mice. Mouse-human chimerization of an anti-tetanus toxin MAb improved its in vivo toxin neutralizing activity, implying contribution of the constant region of the MAb in toxin neutralization.