Immunotherapy with human monoclonal antibodies. Fragment A specificity of polyclonal antibodies is crucial for full protection against tetanus toxin

To investigate the feasibility of substituting human mAb (HmAb) for human polyclonal preparations in the treatment of infections, we employed anti-tetanus, toxin (TT) as a model system. We established a large panel of hybridomas secreting anti-TT HmAb and compared their fine specificities and protective with those exhibited by tetanus immune globulin (TIG). Analysis of three different commercial TIG preparations indicated that the majority of anti-TT antibodies is directed against epitopes expressed by the A fragment, the L chain of TT. Absorption of TIG with purified A fragment completely abolished its protective capacity in mice. Absorption with C fragment, the carboxy-terminal portion of the H chain of TT, had no discernible effect, illustrating the crucial importance of anti-A fragment antibody.