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Impact of O-Acetylation on S. flexneri 1b and 2a O-Antigen Immunogenicity in Mice

Shigellosis is a diarrheal disease caused prevalently by Shigella flexneri and S. sonnei and representing a major global health risk, particularly in developing countries. Bacterial O-antigen (OAg) is the primary target of the host immune response and modifications of its oligosaccharide units, incl...

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Autores principales: Arato, Vanessa, Oldrini, Davide, Massai, Luisa, Gasperini, Gianmarco, Necchi, Francesca, Micoli, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623282/
https://www.ncbi.nlm.nih.gov/pubmed/34835485
http://dx.doi.org/10.3390/microorganisms9112360
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author Arato, Vanessa
Oldrini, Davide
Massai, Luisa
Gasperini, Gianmarco
Necchi, Francesca
Micoli, Francesca
author_facet Arato, Vanessa
Oldrini, Davide
Massai, Luisa
Gasperini, Gianmarco
Necchi, Francesca
Micoli, Francesca
author_sort Arato, Vanessa
collection PubMed
description Shigellosis is a diarrheal disease caused prevalently by Shigella flexneri and S. sonnei and representing a major global health risk, particularly in developing countries. Bacterial O-antigen (OAg) is the primary target of the host immune response and modifications of its oligosaccharide units, including O-acetylation, are responsible for the variability among the circulating S. flexneri serotypes. No vaccines are widely available against shigellosis and the understanding of the immunogenicity induced by the OAg is fundamental for the design of a vaccine that could cover the most prevalent Shigella serotypes. To understand whether a different O-acetylation pattern could influence the immune response elicited by S. flexneri OAg, we employed as a vaccine technology GMMA purified from S. flexneri 2a and 1b strains that were easily engineered to obtain differently O-acetylated OAg. Resulting GMMA were tested in mice, demonstrating not only no major impact of O-acetyl decorations on the immune response elicited by the two OAg against the homologous strains, but also that the O-acetylation of the Rhamnose III residue (O-factor 9), shared among serotypes 1b, 2a and 6, does not induce cross-reactive antibodies against these serotypes. This work contributes to the optimization of vaccine design against Shigella, providing indication about the ability of shared epitopes to elicit broad protection against S. flexneri serotypes and supporting the identification of critical quality attributes of OAg-based vaccines.
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spelling pubmed-86232822021-11-27 Impact of O-Acetylation on S. flexneri 1b and 2a O-Antigen Immunogenicity in Mice Arato, Vanessa Oldrini, Davide Massai, Luisa Gasperini, Gianmarco Necchi, Francesca Micoli, Francesca Microorganisms Article Shigellosis is a diarrheal disease caused prevalently by Shigella flexneri and S. sonnei and representing a major global health risk, particularly in developing countries. Bacterial O-antigen (OAg) is the primary target of the host immune response and modifications of its oligosaccharide units, including O-acetylation, are responsible for the variability among the circulating S. flexneri serotypes. No vaccines are widely available against shigellosis and the understanding of the immunogenicity induced by the OAg is fundamental for the design of a vaccine that could cover the most prevalent Shigella serotypes. To understand whether a different O-acetylation pattern could influence the immune response elicited by S. flexneri OAg, we employed as a vaccine technology GMMA purified from S. flexneri 2a and 1b strains that were easily engineered to obtain differently O-acetylated OAg. Resulting GMMA were tested in mice, demonstrating not only no major impact of O-acetyl decorations on the immune response elicited by the two OAg against the homologous strains, but also that the O-acetylation of the Rhamnose III residue (O-factor 9), shared among serotypes 1b, 2a and 6, does not induce cross-reactive antibodies against these serotypes. This work contributes to the optimization of vaccine design against Shigella, providing indication about the ability of shared epitopes to elicit broad protection against S. flexneri serotypes and supporting the identification of critical quality attributes of OAg-based vaccines. MDPI 2021-11-15 /pmc/articles/PMC8623282/ /pubmed/34835485 http://dx.doi.org/10.3390/microorganisms9112360 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Arato, Vanessa
Oldrini, Davide
Massai, Luisa
Gasperini, Gianmarco
Necchi, Francesca
Micoli, Francesca
Impact of O-Acetylation on S. flexneri 1b and 2a O-Antigen Immunogenicity in Mice
title Impact of O-Acetylation on S. flexneri 1b and 2a O-Antigen Immunogenicity in Mice
title_full Impact of O-Acetylation on S. flexneri 1b and 2a O-Antigen Immunogenicity in Mice
title_fullStr Impact of O-Acetylation on S. flexneri 1b and 2a O-Antigen Immunogenicity in Mice
title_full_unstemmed Impact of O-Acetylation on S. flexneri 1b and 2a O-Antigen Immunogenicity in Mice
title_short Impact of O-Acetylation on S. flexneri 1b and 2a O-Antigen Immunogenicity in Mice
title_sort impact of o-acetylation on s. flexneri 1b and 2a o-antigen immunogenicity in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623282/
https://www.ncbi.nlm.nih.gov/pubmed/34835485
http://dx.doi.org/10.3390/microorganisms9112360
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