Contribution of Fc fragment of monoclonal antibodies to tetanus toxin neutralization.
F(ab′)2
Fab
Monoclonal antibody
Tetanus toxin
Toxin neutralization
Journal
Neurotoxicity research
ISSN: 1476-3524
Titre abrégé: Neurotox Res
Pays: United States
ID NLM: 100929017
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
27
03
2019
accepted:
11
10
2019
revised:
08
10
2019
pubmed:
14
11
2019
medline:
15
12
2020
entrez:
14
11
2019
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 31721050
doi: 10.1007/s12640-019-00124-9
pii: 10.1007/s12640-019-00124-9
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Immunoglobulin Fc Fragments
0
Tetanus Toxin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
578-586Références
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