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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC4526226?pdf=render |
| _version_ | 1819129479754153984 |
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| author | Amit Kumar Mike Hays Francis Lim Leonard J Foster Mingxu Zhou Guoqiang Zhu Tracy Miesner Philip R Hardwidge |
| author_facet | Amit Kumar Mike Hays Francis Lim Leonard J Foster Mingxu Zhou Guoqiang Zhu Tracy Miesner Philip R Hardwidge |
| author_sort | Amit Kumar |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T08:44:23Z |
| format | Article |
| id | doaj.art-e8377edfcab04e0892749ff9225a470b |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-22T08:44:23Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-e8377edfcab04e0892749ff9225a470b2022-12-21T18:32:09ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352015-01-0198e000392410.1371/journal.pntd.0003924Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model.Amit KumarMike HaysFrancis LimLeonard J FosterMingxu ZhouGuoqiang ZhuTracy MiesnerPhilip R HardwidgeEnterotoxigenic 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.http://europepmc.org/articles/PMC4526226?pdf=render |
| spellingShingle | Amit Kumar Mike Hays Francis Lim Leonard J Foster Mingxu Zhou Guoqiang Zhu Tracy Miesner Philip R Hardwidge Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model. PLoS Neglected Tropical Diseases |
| 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 |
| url | http://europepmc.org/articles/PMC4526226?pdf=render |
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