Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA)

Abstract GMMA are exosomes released from engineered Gram-negative bacteria resembling the composition of outer membranes. We applied the GMMA technology for the development of an O-Antigen (OAg) based vaccine against Shigella sonnei, the most epidemiologically relevant cause of shigellosis. S. sonne...

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Autores principales:	Francesca Mancini, Gianmarco Gasperini, Omar Rossi, Maria Grazia Aruta, Maria Michelina Raso, Renzo Alfini, Massimiliano Biagini, Francesca Necchi, Francesca Micoli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0a9858c796534422bc600eb1b85c85dd
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spelling	oai:doaj.org-article:0a9858c796534422bc600eb1b85c85dd2021-12-02T14:12:10ZDissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA)10.1038/s41598-020-80421-y2045-2322https://doaj.org/article/0a9858c796534422bc600eb1b85c85dd2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80421-yhttps://doaj.org/toc/2045-2322Abstract GMMA are exosomes released from engineered Gram-negative bacteria resembling the composition of outer membranes. We applied the GMMA technology for the development of an O-Antigen (OAg) based vaccine against Shigella sonnei, the most epidemiologically relevant cause of shigellosis. S. sonnei OAg has been identified as a key antigen for protective immunity, and GMMA are able to induce anti-OAg-specific IgG response in animal models and healthy adults. The contribution of protein-specific antibodies induced upon vaccination with GMMA has never been fully elucidated. Anti-protein antibodies are induced in mice upon immunization with either OAg-negative and OAg-positive GMMA. Here we demonstrated that OAg chains shield the bacteria from anti-protein antibody binding and therefore anti-OAg antibodies were the main drivers of bactericidal activity against OAg-positive bacteria. Interestingly, antibodies that are not targeting the OAg are functional against OAg-negative bacteria. The immunodominant protein antigens were identified by proteomic analysis. Our study confirms a critical role of the OAg on the immune response induced by S. sonnei GMMA. However, little is known about OAg length and density regulation during infection and, therefore, protein exposure. Hence, the presence of protein antigens on S. sonnei GMMA represents an added value for GMMA vaccines compared to other OAg-based formulations.Francesca ManciniGianmarco GasperiniOmar RossiMaria Grazia ArutaMaria Michelina RasoRenzo AlfiniMassimiliano BiaginiFrancesca NecchiFrancesca MicoliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francesca Mancini Gianmarco Gasperini Omar Rossi Maria Grazia Aruta Maria Michelina Raso Renzo Alfini Massimiliano Biagini Francesca Necchi Francesca Micoli Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA)
description	Abstract GMMA are exosomes released from engineered Gram-negative bacteria resembling the composition of outer membranes. We applied the GMMA technology for the development of an O-Antigen (OAg) based vaccine against Shigella sonnei, the most epidemiologically relevant cause of shigellosis. S. sonnei OAg has been identified as a key antigen for protective immunity, and GMMA are able to induce anti-OAg-specific IgG response in animal models and healthy adults. The contribution of protein-specific antibodies induced upon vaccination with GMMA has never been fully elucidated. Anti-protein antibodies are induced in mice upon immunization with either OAg-negative and OAg-positive GMMA. Here we demonstrated that OAg chains shield the bacteria from anti-protein antibody binding and therefore anti-OAg antibodies were the main drivers of bactericidal activity against OAg-positive bacteria. Interestingly, antibodies that are not targeting the OAg are functional against OAg-negative bacteria. The immunodominant protein antigens were identified by proteomic analysis. Our study confirms a critical role of the OAg on the immune response induced by S. sonnei GMMA. However, little is known about OAg length and density regulation during infection and, therefore, protein exposure. Hence, the presence of protein antigens on S. sonnei GMMA represents an added value for GMMA vaccines compared to other OAg-based formulations.
format	article
author	Francesca Mancini Gianmarco Gasperini Omar Rossi Maria Grazia Aruta Maria Michelina Raso Renzo Alfini Massimiliano Biagini Francesca Necchi Francesca Micoli
author_facet	Francesca Mancini Gianmarco Gasperini Omar Rossi Maria Grazia Aruta Maria Michelina Raso Renzo Alfini Massimiliano Biagini Francesca Necchi Francesca Micoli
author_sort	Francesca Mancini
title	Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA)
title_short	Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA)
title_full	Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA)
title_fullStr	Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA)
title_full_unstemmed	Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA)
title_sort	dissecting the contribution of o-antigen and proteins to the immunogenicity of shigella sonnei generalized modules for membrane antigens (gmma)
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0a9858c796534422bc600eb1b85c85dd
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Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA)

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