Analysis of the immune response to papain digestion products of tetanus toxin.

Tetanus toxin was degraded by papain and the previously characterized Fragment B and Fragment C were isolated. The induction of protective immunity against tetanus toxin was subsequently investigated in two animal models using Fragment B and Fragment C, as well as conventional tetanus toxoid for comparison. In guinea pigs, Fragment B showed an immunizing potency similar to that recorded for an equal amount of tetanus toxoid, whereas Fragment C was considerably less efficient, on an equal weight basis. In contrast, mice immunized with Fragment C reached a protection level similar to that achieved after immunization with the complete tetanus toxoid antigen. In both animal models, Fragments B and C acted in a synergistic fashion when injected together. Analysis of sera from guinea pigs using ELISA, after administration of a low dose of tetanus immunogen corroborated these results. The data indicate that antigenic determinants in distinct regions of the toxin molecule independently may induce antibodies neutralizing the lethal action of tetanus toxin. The immune response to the complete toxoid antigen may be subject to influence by intramolecular competition between antigenic determinants. The immunogenicity of the fragments as measured by the protection rate after active immunization may depend upon the animal species used.