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Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model

Enterotoxigenic Escherichia coli (ETEC) is an endemic health threat in underdeveloped nations. Despite the significant effort extended to vaccine trials using ETEC colonization factors, these approaches have generally not been especially effective in mediating cross-protective immunity. We used quan...

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Autores principales: Kumar, Amit, Hays, Mike, Lim, Francis, Foster, Leonard J., Zhou, Mingxu, Zhu, Guoqiang, Miesner, Tracy, Hardwidge, Philip R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526226/
https://www.ncbi.nlm.nih.gov/pubmed/26244636
http://dx.doi.org/10.1371/journal.pntd.0003924
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author Kumar, Amit
Hays, Mike
Lim, Francis
Foster, Leonard J.
Zhou, Mingxu
Zhu, Guoqiang
Miesner, Tracy
Hardwidge, Philip R.
author_facet Kumar, Amit
Hays, Mike
Lim, Francis
Foster, Leonard J.
Zhou, Mingxu
Zhu, Guoqiang
Miesner, Tracy
Hardwidge, Philip R.
author_sort Kumar, Amit
collection PubMed
description Enterotoxigenic Escherichia coli (ETEC) is an endemic health threat in underdeveloped nations. Despite the significant effort extended to vaccine trials using ETEC colonization factors, these approaches have generally not been especially effective in mediating cross-protective immunity. We used quantitative proteomics to identify 24 proteins that differed in abundance in membrane protein preparations derived from wild-type vs. a type II secretion system mutant of ETEC. We expressed and purified a subset of these proteins and identified nine antigens that generated significant immune responses in mice. Sera from mice immunized with either the MltA-interacting protein MipA, the periplasmic chaperone seventeen kilodalton protein, Skp, or a long-chain fatty acid outer membrane transporter, ETEC_2479, reduced the adherence of multiple ETEC strains differing in colonization factor expression to human intestinal epithelial cells. In intranasal challenge assays of mice, immunization with ETEC_2479 protected 88% of mice from an otherwise lethal challenge with ETEC H10407. Immunization with either Skp or MipA provided an intermediate degree of protection, 68 and 64%, respectively. Protection was significantly correlated with the induction of a secretory immunoglobulin A response. This study has identified several proteins that are conserved among heterologous ETEC strains and may thus potentially improve cross-protective efficacy if incorporated into future vaccine designs.
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spelling pubmed-45262262015-08-12 Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model Kumar, Amit Hays, Mike Lim, Francis Foster, Leonard J. Zhou, Mingxu Zhu, Guoqiang Miesner, Tracy Hardwidge, Philip R. PLoS Negl Trop Dis Research Article Enterotoxigenic Escherichia coli (ETEC) is an endemic health threat in underdeveloped nations. Despite the significant effort extended to vaccine trials using ETEC colonization factors, these approaches have generally not been especially effective in mediating cross-protective immunity. We used quantitative proteomics to identify 24 proteins that differed in abundance in membrane protein preparations derived from wild-type vs. a type II secretion system mutant of ETEC. We expressed and purified a subset of these proteins and identified nine antigens that generated significant immune responses in mice. Sera from mice immunized with either the MltA-interacting protein MipA, the periplasmic chaperone seventeen kilodalton protein, Skp, or a long-chain fatty acid outer membrane transporter, ETEC_2479, reduced the adherence of multiple ETEC strains differing in colonization factor expression to human intestinal epithelial cells. In intranasal challenge assays of mice, immunization with ETEC_2479 protected 88% of mice from an otherwise lethal challenge with ETEC H10407. Immunization with either Skp or MipA provided an intermediate degree of protection, 68 and 64%, respectively. Protection was significantly correlated with the induction of a secretory immunoglobulin A response. This study has identified several proteins that are conserved among heterologous ETEC strains and may thus potentially improve cross-protective efficacy if incorporated into future vaccine designs. Public Library of Science 2015-08-05 /pmc/articles/PMC4526226/ /pubmed/26244636 http://dx.doi.org/10.1371/journal.pntd.0003924 Text en © 2015 Kumar et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kumar, Amit
Hays, Mike
Lim, Francis
Foster, Leonard J.
Zhou, Mingxu
Zhu, Guoqiang
Miesner, Tracy
Hardwidge, Philip R.
Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model
title Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model
title_full Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model
title_fullStr Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model
title_full_unstemmed Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model
title_short Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model
title_sort protective enterotoxigenic escherichia coli antigens in a murine intranasal challenge model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526226/
https://www.ncbi.nlm.nih.gov/pubmed/26244636
http://dx.doi.org/10.1371/journal.pntd.0003924
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