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Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model

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dc.citation.doi10.1371/journal.pntd.0003924
dc.citation.issn1935-2735
dc.citation.issue8
dc.citation.jtitlePLoS Neglected Tropical Diseases
dc.citation.spage16
dc.citation.volume9
dc.contributor.authorKumar, A.
dc.contributor.authorHays, M.
dc.contributor.authorLim, F.
dc.contributor.authorFoster, L. J.
dc.contributor.authorZhou, M. X.
dc.contributor.authorZhu, G. Q.
dc.contributor.authorMiesner, T.
dc.contributor.authorHardwidge, Philip R.
dc.contributor.authoreidphiliphardwidge
dc.date.accessioned2016-04-04T22:44:53Z
dc.date.available2016-04-04T22:44:53Z
dc.date.issued2015-08-05
dc.date.published2015
dc.descriptionCitation: Kumar, A., Hays, M., Lim, F., Foster, L. J., Zhou, M. X., Zhu, G. Q., . . . Hardwidge, P. R. (2015). Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model. Plos Neglected Tropical Diseases, 9(8), 16. doi:10.1371/journal.pntd.0003924
dc.descriptionEnterotoxigenic 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.
dc.identifier.urihttp://hdl.handle.net/2097/32278
dc.relation.urihttps://doi.org/10.1371/journal.pntd.0003924
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHeat-Labile Enterotoxin
dc.subjectOuter-Membrane Protein
dc.subjectPutative Colonization
dc.subjectFactor
dc.subjectB-Subunit Vaccine
dc.subjectCombination Vaccine
dc.titleProtective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model
dc.typeArticle

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