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

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...

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Autores principales: Mancini, Francesca, Gasperini, Gianmarco, Rossi, Omar, Aruta, Maria Grazia, Raso, Maria Michelina, Alfini, Renzo, Biagini, Massimiliano, Necchi, Francesca, Micoli, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806729/
https://www.ncbi.nlm.nih.gov/pubmed/33441861
http://dx.doi.org/10.1038/s41598-020-80421-y
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author Mancini, Francesca
Gasperini, Gianmarco
Rossi, Omar
Aruta, Maria Grazia
Raso, Maria Michelina
Alfini, Renzo
Biagini, Massimiliano
Necchi, Francesca
Micoli, Francesca
author_facet Mancini, Francesca
Gasperini, Gianmarco
Rossi, Omar
Aruta, Maria Grazia
Raso, Maria Michelina
Alfini, Renzo
Biagini, Massimiliano
Necchi, Francesca
Micoli, Francesca
author_sort Mancini, Francesca
collection PubMed
description 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.
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spelling pubmed-78067292021-01-14 Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA) Mancini, Francesca Gasperini, Gianmarco Rossi, Omar Aruta, Maria Grazia Raso, Maria Michelina Alfini, Renzo Biagini, Massimiliano Necchi, Francesca Micoli, Francesca Sci Rep Article 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. Nature Publishing Group UK 2021-01-13 /pmc/articles/PMC7806729/ /pubmed/33441861 http://dx.doi.org/10.1038/s41598-020-80421-y Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mancini, Francesca
Gasperini, Gianmarco
Rossi, Omar
Aruta, Maria Grazia
Raso, Maria Michelina
Alfini, Renzo
Biagini, Massimiliano
Necchi, Francesca
Micoli, Francesca
Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA)
title 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_short 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)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806729/
https://www.ncbi.nlm.nih.gov/pubmed/33441861
http://dx.doi.org/10.1038/s41598-020-80421-y
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