Impact of O-Acetylation on <i>S. flexneri</i> 1b and 2a O-Antigen Immunogenicity in Mice
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 modificati...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/11/2360 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:14:46Z |
| format | Article |
| id | doaj.art-6c2d235a723a49bb93a91981c21a43de |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T05:14:46Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-6c2d235a723a49bb93a91981c21a43de2023-11-23T00:30:16ZengMDPI AGMicroorganisms2076-26072021-11-01911236010.3390/microorganisms9112360Impact of O-Acetylation on <i>S. flexneri</i> 1b and 2a O-Antigen Immunogenicity in MiceVanessa Arato0Davide Oldrini1Luisa Massai2Gianmarco Gasperini3Francesca Necchi4Francesca Micoli5GSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyGSK Vaccines Institute for Global Health, 53100 Siena, ItalyShigellosis 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.https://www.mdpi.com/2076-2607/9/11/2360<i>Shigella flexneri</i>O-antigenO-acetylationGMMA vaccine |
| spellingShingle | 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 Microorganisms <i>Shigella flexneri</i> O-antigen O-acetylation GMMA vaccine |
| title | 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_short | 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 |
| topic | <i>Shigella flexneri</i> O-antigen O-acetylation GMMA vaccine |
| url | https://www.mdpi.com/2076-2607/9/11/2360 |
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