A Highly Effective Component Vaccine against Nontyphoidal <named-content content-type="genus-species">Salmonella enterica</named-content> Infections

ABSTRACT Nontyphoidal Salmonella enterica (NTS) infections are a major burden to global public health, as they lead to diseases ranging from gastroenteritis to systemic infections and there is currently no vaccine available. Here, we describe a highly effective component vaccine against S. enterica...

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Autores principales:	Rosana B. R. Ferreira, Yanet Valdez, Brian K. Coombes, Subash Sad, Joost W. Gouw, Eric M. Brown, Yuling Li, Guntram A. Grassl, L. Caetano M. Antunes, Navkiran Gill, Mimi Truong, Roland Scholz, Lisa A. Reynolds, Laskshmi Krishnan, Ahmed A. Zafer, Neta Sal-Man, Michael J. Lowden, Sigrid D. Auweter, Leonard J. Foster, B. Brett Finlay
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ac70c9215c0d45ce813794f8a4a04cbb
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spelling	oai:doaj.org-article:ac70c9215c0d45ce813794f8a4a04cbb2021-11-15T15:41:30ZA Highly Effective Component Vaccine against Nontyphoidal <named-content content-type="genus-species">Salmonella enterica</named-content> Infections10.1128/mBio.01421-152150-7511https://doaj.org/article/ac70c9215c0d45ce813794f8a4a04cbb2015-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01421-15https://doaj.org/toc/2150-7511ABSTRACT Nontyphoidal Salmonella enterica (NTS) infections are a major burden to global public health, as they lead to diseases ranging from gastroenteritis to systemic infections and there is currently no vaccine available. Here, we describe a highly effective component vaccine against S. enterica serovar Typhimurium in both gastroenteritis and systemic murine infection models. We devised an approach to generate supernatants of S. enterica serovar Typhimurium, an organism that is highly abundant in virulence factors. Immunization of mice with this supernatant resulted in dramatic protection against a challenge with serovar Typhimurium, showing increased survival in the systemic model and decreased intestinal pathology in the gastrointestinal model. Protection correlated with specific IgA and IgG levels in the serum and specific secretory IgA levels in the feces of immunized mice. Initial characterization of the protective antigens in the bacterial culture supernatants revealed a subset of antigens that exhibited remarkable stability, a highly desirable characteristic of an effective vaccine to be used under suboptimal environmental conditions in developing countries. We were able to purify a subset of the peptides present in the supernatants and show their potential for immunization of mice against serovar Typhimurium resulting in a decreased level of colonization. This component vaccine shows promise with regard to protecting against NTS, and further work should significantly help to establish vaccines against these prevalent infections. IMPORTANCE Salmonella enterica infections other than typhoid and paratyphoid fever are a major global health burden, as they cause high morbidity and mortality worldwide. Strategies that prevent Salmonella-related diseases are greatly needed, and there is a significant push for the development of vaccines against nontyphoidal Salmonella enterica serovars. In this work, we describe an S. Typhimurium supernatant-derived vaccine that is effective in reducing bacterial colonization in mouse models of gastroenteritis as well as invasive disease. This is a component vaccine that shows high stability to heat, a feature that is important for use under suboptimal conditions, such as those found in sub-Saharan Africa.Rosana B. R. FerreiraYanet ValdezBrian K. CoombesSubash SadJoost W. GouwEric M. BrownYuling LiGuntram A. GrasslL. Caetano M. AntunesNavkiran GillMimi TruongRoland ScholzLisa A. ReynoldsLaskshmi KrishnanAhmed A. ZaferNeta Sal-ManMichael J. LowdenSigrid D. AuweterLeonard J. FosterB. Brett FinlayAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 5 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Rosana B. R. Ferreira Yanet Valdez Brian K. Coombes Subash Sad Joost W. Gouw Eric M. Brown Yuling Li Guntram A. Grassl L. Caetano M. Antunes Navkiran Gill Mimi Truong Roland Scholz Lisa A. Reynolds Laskshmi Krishnan Ahmed A. Zafer Neta Sal-Man Michael J. Lowden Sigrid D. Auweter Leonard J. Foster B. Brett Finlay A Highly Effective Component Vaccine against Nontyphoidal <named-content content-type="genus-species">Salmonella enterica</named-content> Infections
description	ABSTRACT Nontyphoidal Salmonella enterica (NTS) infections are a major burden to global public health, as they lead to diseases ranging from gastroenteritis to systemic infections and there is currently no vaccine available. Here, we describe a highly effective component vaccine against S. enterica serovar Typhimurium in both gastroenteritis and systemic murine infection models. We devised an approach to generate supernatants of S. enterica serovar Typhimurium, an organism that is highly abundant in virulence factors. Immunization of mice with this supernatant resulted in dramatic protection against a challenge with serovar Typhimurium, showing increased survival in the systemic model and decreased intestinal pathology in the gastrointestinal model. Protection correlated with specific IgA and IgG levels in the serum and specific secretory IgA levels in the feces of immunized mice. Initial characterization of the protective antigens in the bacterial culture supernatants revealed a subset of antigens that exhibited remarkable stability, a highly desirable characteristic of an effective vaccine to be used under suboptimal environmental conditions in developing countries. We were able to purify a subset of the peptides present in the supernatants and show their potential for immunization of mice against serovar Typhimurium resulting in a decreased level of colonization. This component vaccine shows promise with regard to protecting against NTS, and further work should significantly help to establish vaccines against these prevalent infections. IMPORTANCE Salmonella enterica infections other than typhoid and paratyphoid fever are a major global health burden, as they cause high morbidity and mortality worldwide. Strategies that prevent Salmonella-related diseases are greatly needed, and there is a significant push for the development of vaccines against nontyphoidal Salmonella enterica serovars. In this work, we describe an S. Typhimurium supernatant-derived vaccine that is effective in reducing bacterial colonization in mouse models of gastroenteritis as well as invasive disease. This is a component vaccine that shows high stability to heat, a feature that is important for use under suboptimal conditions, such as those found in sub-Saharan Africa.
format	article
author	Rosana B. R. Ferreira Yanet Valdez Brian K. Coombes Subash Sad Joost W. Gouw Eric M. Brown Yuling Li Guntram A. Grassl L. Caetano M. Antunes Navkiran Gill Mimi Truong Roland Scholz Lisa A. Reynolds Laskshmi Krishnan Ahmed A. Zafer Neta Sal-Man Michael J. Lowden Sigrid D. Auweter Leonard J. Foster B. Brett Finlay
author_facet	Rosana B. R. Ferreira Yanet Valdez Brian K. Coombes Subash Sad Joost W. Gouw Eric M. Brown Yuling Li Guntram A. Grassl L. Caetano M. Antunes Navkiran Gill Mimi Truong Roland Scholz Lisa A. Reynolds Laskshmi Krishnan Ahmed A. Zafer Neta Sal-Man Michael J. Lowden Sigrid D. Auweter Leonard J. Foster B. Brett Finlay
author_sort	Rosana B. R. Ferreira
title	A Highly Effective Component Vaccine against Nontyphoidal <named-content content-type="genus-species">Salmonella enterica</named-content> Infections
title_short	A Highly Effective Component Vaccine against Nontyphoidal <named-content content-type="genus-species">Salmonella enterica</named-content> Infections
title_full	A Highly Effective Component Vaccine against Nontyphoidal <named-content content-type="genus-species">Salmonella enterica</named-content> Infections
title_fullStr	A Highly Effective Component Vaccine against Nontyphoidal <named-content content-type="genus-species">Salmonella enterica</named-content> Infections
title_full_unstemmed	A Highly Effective Component Vaccine against Nontyphoidal <named-content content-type="genus-species">Salmonella enterica</named-content> Infections
title_sort	highly effective component vaccine against nontyphoidal <named-content content-type="genus-species">salmonella enterica</named-content> infections
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/ac70c9215c0d45ce813794f8a4a04cbb
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A Highly Effective Component Vaccine against Nontyphoidal <named-content content-type="genus-species">Salmonella enterica</named-content> Infections

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