Application of Anti-Tetanus Human Monoclonal Antibodies

Abstract

To develop anti-tetanus human monoclonal antibodies (MAbs) applicable for clinical use, five hybrid cell lines (human lymphocytes-a mouse/human heteromyeloma SHM-D33 or RF-S1) stably producing human MAbs with high toxin-neutralizing activity in large amounts in serum-free medium were established. The MAbs they produced were the IgG type, had very high affinity (Ka ca. 10¹¹ M^-1) and were directed against one of the three domains [A], [B] or [C] of the tetanus toxin molecule. Their protective effects were studied in comparison with that of polyclonal antibody by observing the effects on progress of tetanus symptoms of mice. Mice injected im with toxin pretreated in vitro with the individual MAbs above sufficient doses survived, although at doses below the sufficient doses, delayed intoxication and progress of symptoms over 96 h and delayed death of the mice were observed. Injection iv of the individual MAbs or their mixtures at over doses equivalent to 0.03~0.1 IU per mouse protected from subsequent challenge with 20 MLD of toxin. Mice injected im with 4 MLD of toxin could be protected by iv injection of individual MAbs or mixture at doses equivalent to 0.03 IU per mouse, even 10 h after injection of toxin. Thus these human MAbs should be useful for prevention and treatment of human tetanus.