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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ftdoajarticles:oai:doaj.org/article:636724f9ceda4c73b69c495101a7c4cc 2023-05-15T15:12:36+02:00 Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes. 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 2021-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0009826 https://doaj.org/article/636724f9ceda4c73b69c495101a7c4cc EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0009826 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009826 https://doaj.org/article/636724f9ceda4c73b69c495101a7c4cc PLoS Neglected Tropical Diseases, Vol 15, Iss 10, p e0009826 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0009826 2022-12-31T15:49:17Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 15 10 e0009826 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
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. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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 in Journal/Newspaper |
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://doi.org/10.1371/journal.pntd.0009826 https://doaj.org/article/636724f9ceda4c73b69c495101a7c4cc |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 10, p e0009826 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0009826 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009826 https://doaj.org/article/636724f9ceda4c73b69c495101a7c4cc |
op_doi |
https://doi.org/10.1371/journal.pntd.0009826 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
15 |
container_issue |
10 |
container_start_page |
e0009826 |
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1766343266884648960 |