Anti-Tetanus Human Monoclonal Antibodies-Comparative Studies on Their Protective Activity with Polyclonal Antibody

Abstract

We established five stable hybrid cell lines producing anti-tetanus human monoclonal antibodies (MAbs) with high neutralizing activity. The protective activity was studied in vitro and in vivo in comparison with that of human polyclonal antibody currently used clinicaly. Mice, injected intramuscularly (im) with toxin pretreated in vitro with the individual MAbs above sufficient doses, survived. At doses below those sufficient to rescue mice, the kinetic patterns of the changes in the progress of tetanus symptoms with the individual MAbs differed each other and were different from that of anti-tetanus human polyclonal antibody: delayed intoxication and progress of symptoms over 96 h and delayed death of mice were observed. Intravenously (iv) injection of the individual MAbs or human polyclonal antibody at over 0.03 IU per mouse protected mice from subsequent challenges with 20 MLD of toxin. Moreover, mice injected im with 4 MLD of toxin could be protected by iv injection of individual MAbs or human polyclonal antibody (at doses equivalent to 0.03 IU per mouse), even 10 h after injection of toxin. These curative effects of MAbs were comparable to that of human polyclonal antibody. Thus these human MAbs should be useful for the prevention and treatment of human tetanus.