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The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections

Eliminating diarrheal diseases as a leading cause of childhood morbidity and mortality in low- and middle-income countries (LMICs) will require multiple intervention strategies. In this review, we spotlight a series of preclinical studies investigating the potential of orally administered monoclonal...

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Autores principales: Richards, Angelene, Baranova, Danielle, Mantis, Nicholas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103515/
https://www.ncbi.nlm.nih.gov/pubmed/34491878
http://dx.doi.org/10.1080/21645515.2021.1964317
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author Richards, Angelene
Baranova, Danielle
Mantis, Nicholas J.
author_facet Richards, Angelene
Baranova, Danielle
Mantis, Nicholas J.
author_sort Richards, Angelene
collection PubMed
description Eliminating diarrheal diseases as a leading cause of childhood morbidity and mortality in low- and middle-income countries (LMICs) will require multiple intervention strategies. In this review, we spotlight a series of preclinical studies investigating the potential of orally administered monoclonal secretory IgA (SIgA) antibodies (MAbs) to reduce disease associated with three enteric bacterial pathogens: Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC), and invasive Salmonella enterica serovar Typhimurium. IgA MAbs targeting bacterial surface antigens (flagella, adhesins, and lipopolysaccharide) were generated from mice, humanized mice, and human tonsillar B cells. Recombinant SIgA1 and/or SIgA2 derivates of those MAbs were purified from supernatants following transient transfection of 293 cells with plasmids encoding antibody heavy and light chains, J-chain, and secretory component (SC). When administered to mice by gavage immediately prior to (or admixed with) the bacterial challenge, SIgA MAbs reduced infection C. jejuni, ETEC, and S. Typhimurium infections. Fv-matched IgG1 MAbs by comparison were largely ineffective against C. jejuni and S. Typhimurium under the same conditions, although they were partially effective against ETEC. While these findings highlight future applications of orally administered SIgA, the studies also underscored the fundamental challenges associated with using MAbs as prophylactic tools against enteric bacterial diseases.
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spelling pubmed-91035152022-05-14 The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections Richards, Angelene Baranova, Danielle Mantis, Nicholas J. Hum Vaccin Immunother Passive SF – Reviews Eliminating diarrheal diseases as a leading cause of childhood morbidity and mortality in low- and middle-income countries (LMICs) will require multiple intervention strategies. In this review, we spotlight a series of preclinical studies investigating the potential of orally administered monoclonal secretory IgA (SIgA) antibodies (MAbs) to reduce disease associated with three enteric bacterial pathogens: Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC), and invasive Salmonella enterica serovar Typhimurium. IgA MAbs targeting bacterial surface antigens (flagella, adhesins, and lipopolysaccharide) were generated from mice, humanized mice, and human tonsillar B cells. Recombinant SIgA1 and/or SIgA2 derivates of those MAbs were purified from supernatants following transient transfection of 293 cells with plasmids encoding antibody heavy and light chains, J-chain, and secretory component (SC). When administered to mice by gavage immediately prior to (or admixed with) the bacterial challenge, SIgA MAbs reduced infection C. jejuni, ETEC, and S. Typhimurium infections. Fv-matched IgG1 MAbs by comparison were largely ineffective against C. jejuni and S. Typhimurium under the same conditions, although they were partially effective against ETEC. While these findings highlight future applications of orally administered SIgA, the studies also underscored the fundamental challenges associated with using MAbs as prophylactic tools against enteric bacterial diseases. Taylor & Francis 2021-09-07 /pmc/articles/PMC9103515/ /pubmed/34491878 http://dx.doi.org/10.1080/21645515.2021.1964317 Text en © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
spellingShingle Passive SF – Reviews
Richards, Angelene
Baranova, Danielle
Mantis, Nicholas J.
The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections
title The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections
title_full The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections
title_fullStr The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections
title_full_unstemmed The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections
title_short The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections
title_sort prospect of orally administered monoclonal secretory iga (siga) antibodies to prevent enteric bacterial infections
topic Passive SF – Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103515/
https://www.ncbi.nlm.nih.gov/pubmed/34491878
http://dx.doi.org/10.1080/21645515.2021.1964317
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