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 modificati...

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Autores principales:	Vanessa Arato, Davide Oldrini, Luisa Massai, Gianmarco Gasperini, Francesca Necchi, Francesca Micoli
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Shigella flexneri</i> O-antigen O-acetylation GMMA vaccine Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6c2d235a723a49bb93a91981c21a43de
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id	oai:doaj.org-article:6c2d235a723a49bb93a91981c21a43de
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spelling	oai:doaj.org-article:6c2d235a723a49bb93a91981c21a43de2021-11-25T18:25:25ZImpact of O-Acetylation on <i>S. flexneri</i> 1b and 2a O-Antigen Immunogenicity in Mice10.3390/microorganisms91123602076-2607https://doaj.org/article/6c2d235a723a49bb93a91981c21a43de2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-2607/9/11/2360https://doaj.org/toc/2076-2607Shigellosis is a diarrheal disease caused prevalently by <i>Shigella flexneri</i> and <i>S. sonnei</i> 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 <i>S. flexneri</i> 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 <i>Shigella</i> serotypes. To understand whether a different O-acetylation pattern could influence the immune response elicited by <i>S. flexneri</i> OAg, we employed as a vaccine technology GMMA purified from <i>S. flexneri</i> 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 <i>Shigella</i>, providing indication about the ability of shared epitopes to elicit broad protection against <i>S. flexneri</i> serotypes and supporting the identification of critical quality attributes of OAg-based vaccines.Vanessa AratoDavide OldriniLuisa MassaiGianmarco GasperiniFrancesca NecchiFrancesca MicoliMDPI AGarticle<i>Shigella flexneri</i>O-antigenO-acetylationGMMA vaccineBiology (General)QH301-705.5ENMicroorganisms, Vol 9, Iss 2360, p 2360 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Shigella flexneri</i> O-antigen O-acetylation GMMA vaccine Biology (General) QH301-705.5
spellingShingle	<i>Shigella flexneri</i> O-antigen O-acetylation GMMA vaccine Biology (General) QH301-705.5 Vanessa Arato Davide Oldrini Luisa Massai Gianmarco Gasperini Francesca Necchi Francesca Micoli Impact of O-Acetylation on <i>S. flexneri</i> 1b and 2a O-Antigen Immunogenicity in Mice
description	Shigellosis is a diarrheal disease caused prevalently by <i>Shigella flexneri</i> and <i>S. sonnei</i> 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 <i>S. flexneri</i> 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 <i>Shigella</i> serotypes. To understand whether a different O-acetylation pattern could influence the immune response elicited by <i>S. flexneri</i> OAg, we employed as a vaccine technology GMMA purified from <i>S. flexneri</i> 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 <i>Shigella</i>, providing indication about the ability of shared epitopes to elicit broad protection against <i>S. flexneri</i> serotypes and supporting the identification of critical quality attributes of OAg-based vaccines.
format	article
author	Vanessa Arato Davide Oldrini Luisa Massai Gianmarco Gasperini Francesca Necchi Francesca Micoli
author_facet	Vanessa Arato Davide Oldrini Luisa Massai Gianmarco Gasperini Francesca Necchi Francesca Micoli
author_sort	Vanessa Arato
title	Impact of O-Acetylation on <i>S. flexneri</i> 1b and 2a O-Antigen Immunogenicity in Mice
title_short	Impact of O-Acetylation on <i>S. flexneri</i> 1b and 2a O-Antigen Immunogenicity in Mice
title_full	Impact of O-Acetylation on <i>S. flexneri</i> 1b and 2a O-Antigen Immunogenicity in Mice
title_fullStr	Impact of O-Acetylation on <i>S. flexneri</i> 1b and 2a O-Antigen Immunogenicity in Mice
title_full_unstemmed	Impact of O-Acetylation on <i>S. flexneri</i> 1b and 2a O-Antigen Immunogenicity in Mice
title_sort	impact of o-acetylation on <i>s. flexneri</i> 1b and 2a o-antigen immunogenicity in mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6c2d235a723a49bb93a91981c21a43de
work_keys_str_mv	AT vanessaarato impactofoacetylationonisflexnerii1band2aoantigenimmunogenicityinmice AT davideoldrini impactofoacetylationonisflexnerii1band2aoantigenimmunogenicityinmice AT luisamassai impactofoacetylationonisflexnerii1band2aoantigenimmunogenicityinmice AT gianmarcogasperini impactofoacetylationonisflexnerii1band2aoantigenimmunogenicityinmice AT francescanecchi impactofoacetylationonisflexnerii1band2aoantigenimmunogenicityinmice AT francescamicoli impactofoacetylationonisflexnerii1band2aoantigenimmunogenicityinmice
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Impact of O-Acetylation on <i>S. flexneri</i> 1b and 2a O-Antigen Immunogenicity in Mice

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