title: Protective Enterotoxigenic Escherichia coli Antigens in a Murine Intranasal Challenge Model.
abstract: 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.
authors.affiliation: College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, United States of America.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, United States of America.
authors.forename: Mike
authors.initials: M
authors.lastname: Hays
authors.affiliation: Department of Biochemistry & Molecular Biology and Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Francis
authors.initials: F
authors.lastname: Lim
authors.affiliation: Department of Biochemistry & Molecular Biology and Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Foster
authors.affiliation: College of Veterinary Medicine, Yangzhou University and Jiangsu Co-Innovation Center for Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, China.
authors.forename: Mingxu
authors.initials: M
authors.lastname: Zhou
authors.affiliation: College of Veterinary Medicine, Yangzhou University and Jiangsu Co-Innovation Center for Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhu
authors.affiliation: College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, United States of America.
authors.forename: Tracy
authors.initials: T
authors.lastname: Miesner
authors.affiliation: College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, United States of America.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Hardwidge
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D054307:Enterotoxigenic Escherichia coli / Q000235:genetics / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines