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Contribution of Fc fragment of monoclonal antibodies to tetanus toxin neutralization

  • Somayeh Ghotloo
  • Mohammad Mehdi Amiri
  • Jalal Khoshnoodi
  • Ebrahim Abbasi
  • Mahmood Jeddi-Tehrani
  • Forough Golsaz-Shirazi
  • Fazel ShokriEmail author
Original Article
  • 39 Downloads

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords

Fab F(ab′)2 Monoclonal antibody Tetanus toxin Toxin neutralization 

Notes

Acknowledgements

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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Immunology, School of Public HealthTehran University of Medical SciencesTehranIran
  2. 2.Department of Bacterial VaccinesRazi Vaccine and Serum Research InstituteKarajIran
  3. 3.Monoclonal Antibody Research CenterAvicenna Research Institute, ACECRTehranIran

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