Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes.

No vaccine to protect against an estimated 238,000 shigellosis deaths per year is widely available. S. sonnei is the most prevalent Shigella, and multiple serotypes of S. flexneri, which change regionally and globally, also cause significant disease. The leading Shigella vaccine strategies are based...

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Autores principales:	Francesco Citiulo, Francesca Necchi, Francesca Mancini, Omar Rossi, Maria Grazia Aruta, Gianmarco Gasperini, Renzo Alfini, Simona Rondini, Francesca Micoli, Rino Rappuoli, Allan Saul, Laura B Martin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/636724f9ceda4c73b69c495101a7c4cc
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spelling	oai:doaj.org-article:636724f9ceda4c73b69c495101a7c4cc2021-12-02T20:23:35ZRationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes.1935-27271935-273510.1371/journal.pntd.0009826https://doaj.org/article/636724f9ceda4c73b69c495101a7c4cc2021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009826https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735No vaccine to protect against an estimated 238,000 shigellosis deaths per year is widely available. S. sonnei is the most prevalent Shigella, and multiple serotypes of S. flexneri, which change regionally and globally, also cause significant disease. The leading Shigella vaccine strategies are based on the delivery of serotype specific O-antigens. A strategy to minimize the complexity of a broadly-protective Shigella vaccine is to combine components from S. sonnei with S. flexneri serotypes that induce antibodies with maximum cross-reactivity between different serotypes. We used the GMMA-technology to immunize animal models and generate antisera against 14 S. flexneri subtypes from 8 different serotypes that were tested for binding to and bactericidal activity against a panel of 11 S. flexneri bacteria lines. Some immunogens induced broadly cross-reactive antibodies that interacted with most of the S. flexneri in the panel, while others induced antibodies with narrower specificity. Most cross-reactivity could not be assigned to modifications of the O-antigen, by glucose, acetate or phosphoethanolamine, common to several of the S. flexneri serotypes. This allowed us to revisit the current dogma of cross-reactivity among S. flexneri serotypes suggesting that a broadly protective vaccine is feasible with limited number of appropriately selected components. Thus, we rationally designed a 4-component vaccine selecting GMMA from S. sonnei and S. flexneri 1b, 2a and 3a. The resulting formulation was broadly cross-reactive in mice and rabbits, inducing antibodies that killed all S. flexneri serotypes tested. This study provides the framework for a broadly-protective Shigella vaccine which needs to be verified in human trials.Francesco CitiuloFrancesca NecchiFrancesca ManciniOmar RossiMaria Grazia ArutaGianmarco GasperiniRenzo AlfiniSimona RondiniFrancesca MicoliRino RappuoliAllan SaulLaura B MartinPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 10, p e0009826 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Francesco Citiulo Francesca Necchi Francesca Mancini Omar Rossi Maria Grazia Aruta Gianmarco Gasperini Renzo Alfini Simona Rondini Francesca Micoli Rino Rappuoli Allan Saul Laura B Martin Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes.
description	No vaccine to protect against an estimated 238,000 shigellosis deaths per year is widely available. S. sonnei is the most prevalent Shigella, and multiple serotypes of S. flexneri, which change regionally and globally, also cause significant disease. The leading Shigella vaccine strategies are based on the delivery of serotype specific O-antigens. A strategy to minimize the complexity of a broadly-protective Shigella vaccine is to combine components from S. sonnei with S. flexneri serotypes that induce antibodies with maximum cross-reactivity between different serotypes. We used the GMMA-technology to immunize animal models and generate antisera against 14 S. flexneri subtypes from 8 different serotypes that were tested for binding to and bactericidal activity against a panel of 11 S. flexneri bacteria lines. Some immunogens induced broadly cross-reactive antibodies that interacted with most of the S. flexneri in the panel, while others induced antibodies with narrower specificity. Most cross-reactivity could not be assigned to modifications of the O-antigen, by glucose, acetate or phosphoethanolamine, common to several of the S. flexneri serotypes. This allowed us to revisit the current dogma of cross-reactivity among S. flexneri serotypes suggesting that a broadly protective vaccine is feasible with limited number of appropriately selected components. Thus, we rationally designed a 4-component vaccine selecting GMMA from S. sonnei and S. flexneri 1b, 2a and 3a. The resulting formulation was broadly cross-reactive in mice and rabbits, inducing antibodies that killed all S. flexneri serotypes tested. This study provides the framework for a broadly-protective Shigella vaccine which needs to be verified in human trials.
format	article
author	Francesco Citiulo Francesca Necchi Francesca Mancini Omar Rossi Maria Grazia Aruta Gianmarco Gasperini Renzo Alfini Simona Rondini Francesca Micoli Rino Rappuoli Allan Saul Laura B Martin
author_facet	Francesco Citiulo Francesca Necchi Francesca Mancini Omar Rossi Maria Grazia Aruta Gianmarco Gasperini Renzo Alfini Simona Rondini Francesca Micoli Rino Rappuoli Allan Saul Laura B Martin
author_sort	Francesco Citiulo
title	Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes.
title_short	Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes.
title_full	Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes.
title_fullStr	Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes.
title_full_unstemmed	Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes.
title_sort	rationalizing the design of a broad coverage shigella vaccine based on evaluation of immunological cross-reactivity among s. flexneri serotypes.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/636724f9ceda4c73b69c495101a7c4cc
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Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes.

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