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

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Title: Evaluation of a Live Attenuated S. sonnei Vaccine Strain in the Human Enteroid Model
Authors: Giulia Pilla, Tao Wu, Christen Grassel, Jonathan Moon, Jennifer Foulke-Abel, Christoph M. Tang, Eileen M. Barry
Source: Pathogens, Vol 10, Iss 9, p 1079 (2021)
Publisher Information: MDPI AG, 2021.
Publication Year: 2021
Collection: LCC:Medicine
Subject Terms: Shigella sonnei, human enteroids, Shigella vaccine, Medicine
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2076-0817
Relation: https://www.mdpi.com/2076-0817/10/9/1079; https://doaj.org/toc/2076-0817
DOI: 10.3390/pathogens10091079
Access URL: https://doaj.org/article/c79461ec0421489d93f1b7bed99aaaa9
Accession Number: edsdoj.79461ec0421489d93f1b7bed99aaaa9
Database: Directory of Open Access Journals
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  Data: Pathogens, Vol 10, Iss 9, p 1079 (2021)
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  Data: 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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