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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Main Authors: 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
Format: Article
Language:English
Published: American Society for Microbiology 2015-10-01
Series:mBio
Online Access:https://journals.asm.org/doi/10.1128/mBio.01421-15
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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
collection DOAJ
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.
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spelling doaj.art-ac70c9215c0d45ce813794f8a4a04cbb2022-12-21T23:11:50ZengAmerican Society for MicrobiologymBio2150-75112015-10-016510.1128/mBio.01421-15A Highly Effective Component Vaccine against Nontyphoidal <named-content content-type="genus-species">Salmonella enterica</named-content> InfectionsRosana B. R. Ferreira0Yanet Valdez1Brian K. Coombes2Subash Sad3Joost W. Gouw4Eric M. Brown5Yuling Li6Guntram A. Grassl7L. Caetano M. Antunes8Navkiran Gill9Mimi Truong10Roland Scholz11Lisa A. Reynolds12Laskshmi Krishnan13Ahmed A. Zafer14Neta Sal-Man15Michael J. Lowden16Sigrid D. Auweter17Leonard J. Foster18B. Brett Finlay19Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, CanadaCentre for High-Throughput Biology and Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaEscola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilMichael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaNational Research Council Canada, Institute for Biological Sciences, Ottawa, Ontario, CanadaNational Research Council Canada, Institute for Biological Sciences, Ottawa, Ontario, CanadaDepartament of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelMichael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaCentre for High-Throughput Biology and Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, CanadaABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.01421-15
spellingShingle 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
mBio
title 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_short 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
url https://journals.asm.org/doi/10.1128/mBio.01421-15
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