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Relationship between neutralizing and opsonizing monoclonal antibodies against foot-and-mouth disease virus

Previous studies demonstrated that polyclonal antibodies against foot-and-mouth disease virus (FMDV) generated by vaccination can mediate immune functions not only through virus neutralization but also through promoting virus uptake by macrophages and dendritic cells that are otherwise resistant to...

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Autores principales: Summerfield, Artur, Gerber, Heidi, Schmitt, Rebeka, Liniger, Matthias, Grazioli, Santina, Brocchi, Emiliana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9597200/
https://www.ncbi.nlm.nih.gov/pubmed/36311653
http://dx.doi.org/10.3389/fvets.2022.1033276
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author Summerfield, Artur
Gerber, Heidi
Schmitt, Rebeka
Liniger, Matthias
Grazioli, Santina
Brocchi, Emiliana
author_facet Summerfield, Artur
Gerber, Heidi
Schmitt, Rebeka
Liniger, Matthias
Grazioli, Santina
Brocchi, Emiliana
author_sort Summerfield, Artur
collection PubMed
description Previous studies demonstrated that polyclonal antibodies against foot-and-mouth disease virus (FMDV) generated by vaccination can mediate immune functions not only through virus neutralization but also through promoting virus uptake by macrophages and dendritic cells that are otherwise resistant to FMDV infection. This causes abortive infections resulting in activation, enhanced antigen presentation but also cell death. Here we report the use of RAW264.7 cells representing a murine macrophage cells line to characterize opsonizing functions of a collection of monoclonal antibodies (mAbs) against FMDV O and A serotypes. We demonstrate that all neutralizing immunoglobulin G isotype mAbs are able to opsonize FMDV resulting in increased cell death of RAW264.7 cells. In contrast, neutralizing IgM antibodies did not possess this activity. Opsonization was observed with broader reactivity within the serotype when compared to neutralization. Importantly, the anti-O serotype D9 mAb reacting with the continuous epitope within the G-H loop of VP1 that contains the RGD binding site of FMDV, opsonized several FMDV serotypes despite its restricted neutralizing activity within the O serotype. Furthermore, by generating RAW264.7 cells expressing bovine CD32, an easy-to-use cell-based assay system to test for bovine antibody-dependent enhanced infection of FMDV was generated and tested with a collection of sera. The data indicate that opsonizing titers correlated better with vaccine dose when compared to neutralizing titers. On the other hand, neutralization and opsonization titers were similar predictive of protection. We conclude that low avidity interactions are sufficient to mediate Fcγ receptor-mediated immune functions that could contribute to protective immune responses against FMDV.
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spelling pubmed-95972002022-10-27 Relationship between neutralizing and opsonizing monoclonal antibodies against foot-and-mouth disease virus Summerfield, Artur Gerber, Heidi Schmitt, Rebeka Liniger, Matthias Grazioli, Santina Brocchi, Emiliana Front Vet Sci Veterinary Science Previous studies demonstrated that polyclonal antibodies against foot-and-mouth disease virus (FMDV) generated by vaccination can mediate immune functions not only through virus neutralization but also through promoting virus uptake by macrophages and dendritic cells that are otherwise resistant to FMDV infection. This causes abortive infections resulting in activation, enhanced antigen presentation but also cell death. Here we report the use of RAW264.7 cells representing a murine macrophage cells line to characterize opsonizing functions of a collection of monoclonal antibodies (mAbs) against FMDV O and A serotypes. We demonstrate that all neutralizing immunoglobulin G isotype mAbs are able to opsonize FMDV resulting in increased cell death of RAW264.7 cells. In contrast, neutralizing IgM antibodies did not possess this activity. Opsonization was observed with broader reactivity within the serotype when compared to neutralization. Importantly, the anti-O serotype D9 mAb reacting with the continuous epitope within the G-H loop of VP1 that contains the RGD binding site of FMDV, opsonized several FMDV serotypes despite its restricted neutralizing activity within the O serotype. Furthermore, by generating RAW264.7 cells expressing bovine CD32, an easy-to-use cell-based assay system to test for bovine antibody-dependent enhanced infection of FMDV was generated and tested with a collection of sera. The data indicate that opsonizing titers correlated better with vaccine dose when compared to neutralizing titers. On the other hand, neutralization and opsonization titers were similar predictive of protection. We conclude that low avidity interactions are sufficient to mediate Fcγ receptor-mediated immune functions that could contribute to protective immune responses against FMDV. Frontiers Media S.A. 2022-10-12 /pmc/articles/PMC9597200/ /pubmed/36311653 http://dx.doi.org/10.3389/fvets.2022.1033276 Text en Copyright © 2022 Summerfield, Gerber, Schmitt, Liniger, Grazioli and Brocchi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Summerfield, Artur
Gerber, Heidi
Schmitt, Rebeka
Liniger, Matthias
Grazioli, Santina
Brocchi, Emiliana
Relationship between neutralizing and opsonizing monoclonal antibodies against foot-and-mouth disease virus
title Relationship between neutralizing and opsonizing monoclonal antibodies against foot-and-mouth disease virus
title_full Relationship between neutralizing and opsonizing monoclonal antibodies against foot-and-mouth disease virus
title_fullStr Relationship between neutralizing and opsonizing monoclonal antibodies against foot-and-mouth disease virus
title_full_unstemmed Relationship between neutralizing and opsonizing monoclonal antibodies against foot-and-mouth disease virus
title_short Relationship between neutralizing and opsonizing monoclonal antibodies against foot-and-mouth disease virus
title_sort relationship between neutralizing and opsonizing monoclonal antibodies against foot-and-mouth disease virus
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9597200/
https://www.ncbi.nlm.nih.gov/pubmed/36311653
http://dx.doi.org/10.3389/fvets.2022.1033276
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