Contribution of Fc fragment of monoclonal antibodies to tetanus toxin neutralization
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Monoclonal antibodies (MAbs) against neurotoxin of Clostridium tetani are considered as a novel source of immunoglobulins for passive immunotherapy of tetanus. Toxin neutralization is classically attributed to the Fab and F(ab′)2 fragments of antibodies. Herein, we generated Fab and F(ab′)2 fragments of three toxin neutralizing mouse MAbs and compared their neutralizing activities to those of their intact molecules.
Fab and F (ab′)2 fragments of the antibodies were generated by papain and pepsin digestions, respectively, and their toxin neutralizing activities were compared with those of the intact antibodies in an in vivo toxin neutralization assay.
While low doses of the intact MAbs were able to fully protect the mice against tetanus toxin, none of the mice which received Fab or F(ab′)2 fragments survived until day 14, even at the highest administered dose. All mice receiving human polyclonal anti-tetanus immunoglobulin or their fragments were fully protected.
Reduction in toxin neutralization activities of Fab and F(ab′)2 fragments of our MAbs seems to be influenced by their Fc regions. Steric hindrance of the Fc region on the receptor-binding site of the toxin may explain the stronger neutralization of the toxin by the intact MAbs in comparison to their fragments.
KeywordsFab F(ab′)2 Monoclonal antibody Tetanus toxin Toxin neutralization
The authors wish to thank Mr. Mohammad Ali Judaki for technical assistance. This study was partially supported by a grant from Avicenna Research Institute and a studentship from Tehran University of Medical Sciences.
Compliance with Ethical Standards
Conflict of Interests
The authors declare that they have no conflict of interests.
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