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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| Autores principales: | , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/6c2d235a723a49bb93a91981c21a43de |
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| Sumario: | 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. |
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