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Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model

Shigella is a leading cause of bacillary dysentery worldwide, responsible for high death rates especially among children under five in low–middle income countries. Shigella sonnei prevails in high-income countries and is becoming prevalent in industrializing countries, where multi-drug resistant str...

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Autores principales: Pilla, Giulia, Wu, Tao, Grassel, Christen, Moon, Jonathan, Foulke-Abel, Jennifer, Tang, Christoph M., Barry, Eileen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468197/
https://www.ncbi.nlm.nih.gov/pubmed/34578112
http://dx.doi.org/10.3390/pathogens10091079
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author Pilla, Giulia
Wu, Tao
Grassel, Christen
Moon, Jonathan
Foulke-Abel, Jennifer
Tang, Christoph M.
Barry, Eileen M.
author_facet Pilla, Giulia
Wu, Tao
Grassel, Christen
Moon, Jonathan
Foulke-Abel, Jennifer
Tang, Christoph M.
Barry, Eileen M.
author_sort Pilla, Giulia
collection PubMed
description Shigella is a leading cause of bacillary dysentery worldwide, responsible for high death rates especially among children under five in low–middle income countries. Shigella sonnei prevails in high-income countries and is becoming prevalent in industrializing countries, where multi-drug resistant strains have emerged, as a significant public health concern. One strategy to combat drug resistance in S. sonnei is the development of effective vaccines. There is no licensed vaccine against Shigella, and development has been hindered by the lack of an effective small-animal model. In this work, we used human enteroids, for the first time, as a model system to evaluate a plasmid-stabilized S. sonnei live attenuated vaccine strain, CVD 1233-SP, and a multivalent derivative, CVD 1233-SP::CS2-CS3, which expresses antigens from enterotoxigenic Escherichia coli. The strains were also tested for immunogenicity and protective capacity in the guinea pig model, demonstrating their ability to elicit serum and mucosal antibody responses as well as protection against challenge with wild-type S. sonnei. These promising results highlight the utility of enteroids as an innovative preclinical model to evaluate Shigella vaccine candidates, constituting a significant advance for the development of preventative strategies against this important human pathogen.
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spelling pubmed-84681972021-09-27 Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model Pilla, Giulia Wu, Tao Grassel, Christen Moon, Jonathan Foulke-Abel, Jennifer Tang, Christoph M. Barry, Eileen M. Pathogens Article Shigella is a leading cause of bacillary dysentery worldwide, responsible for high death rates especially among children under five in low–middle income countries. Shigella sonnei prevails in high-income countries and is becoming prevalent in industrializing countries, where multi-drug resistant strains have emerged, as a significant public health concern. One strategy to combat drug resistance in S. sonnei is the development of effective vaccines. There is no licensed vaccine against Shigella, and development has been hindered by the lack of an effective small-animal model. In this work, we used human enteroids, for the first time, as a model system to evaluate a plasmid-stabilized S. sonnei live attenuated vaccine strain, CVD 1233-SP, and a multivalent derivative, CVD 1233-SP::CS2-CS3, which expresses antigens from enterotoxigenic Escherichia coli. The strains were also tested for immunogenicity and protective capacity in the guinea pig model, demonstrating their ability to elicit serum and mucosal antibody responses as well as protection against challenge with wild-type S. sonnei. These promising results highlight the utility of enteroids as an innovative preclinical model to evaluate Shigella vaccine candidates, constituting a significant advance for the development of preventative strategies against this important human pathogen. MDPI 2021-08-25 /pmc/articles/PMC8468197/ /pubmed/34578112 http://dx.doi.org/10.3390/pathogens10091079 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pilla, Giulia
Wu, Tao
Grassel, Christen
Moon, Jonathan
Foulke-Abel, Jennifer
Tang, Christoph M.
Barry, Eileen M.
Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model
title Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model
title_full Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model
title_fullStr Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model
title_full_unstemmed Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model
title_short Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model
title_sort evaluation of a live attenuated s. sonnei vaccine strain in the human enteroid model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468197/
https://www.ncbi.nlm.nih.gov/pubmed/34578112
http://dx.doi.org/10.3390/pathogens10091079
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