title: Antibodies derived from an enterotoxigenic Escherichia coli (ETEC) adhesin tip MEFA (multiepitope fusion antigen) against adherence of nine ETEC adhesins: CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS21 and EtpA.
abstract: Diarrhea continues to be a leading cause of death in children younger than 5 years in developing countries. Enterotoxigenic Escherichia coli (ETEC) is a leading bacterial cause of children's diarrhea and travelers' diarrhea. ETEC bacteria initiate diarrheal disease by attaching to host receptors at epithelial cells and colonizing in small intestine. Therefore, preventing ETEC attachment has been considered the first line of defense against ETEC diarrhea. However, developing vaccines effectively against ETEC bacterial attachment encounters challenge because ETEC strains produce over 23 immunologically heterogeneous adhesins. In this study, we applied MEFA (multiepitope fusion antigen) approach to integrate epitopes from adhesin tips or adhesive subunits of CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS21 and EtpA adhesins and to construct an adhesin tip MEFA peptide. We then examined immunogenicity of this tip MEFA in mouse immunization, and assessed potential application of this tip MEFA for ETEC vaccine development. Data showed that mice intraperitoneally immunized with this adhesin tip MEFA developed IgG antibody responses to all nine ETEC adhesins. Moreover, ETEC and E. coli bacteria expressing these nine adhesins, after incubation with serum of the immunized mice, exhibited significant reduction in attachment to Caco-2 cells. These results indicated that anti-adhesin antibodies induced by this adhesin tip MEFA blocked adherence of the most important ETEC adhesins, suggesting this multivalent tip MEFA may be useful for developing a broadly protective anti-adhesin vaccine against ETEC diarrhea.
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, KS, USA.
authors.forename: Rahul M
authors.initials: RM
authors.lastname: Nandre
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, KS, USA.
authors.forename: Xiaosai
authors.initials: X
authors.lastname: Ruan
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, KS, USA.
authors.forename: Qiangde
authors.initials: Q
authors.lastname: Duan
authors.affiliation: Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Sack
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, KS, USA. Electronic address: wpzhang@vet.k-state.edu.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhang
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D001422:Bacterial Adhesion; D018938:Caco-2 Cells; D003967:Diarrhea / Q000517:prevention & control; D054307:Enterotoxigenic Escherichia coli; D000939:Epitopes / Q000276:immunology; D004927:Escherichia coli Infections / Q000517:prevention & control; D022361:Escherichia coli Vaccines / Q000276:immunology*; D005260:Female; D006801:Humans; D000071497:Immunogenicity, Vaccine; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000939:Epitopes; D022361:Escherichia coli Vaccines; D011993:Recombinant Fusion Proteins
keywords: Adhesin tip; Diarrhea; ETEC (enterotoxigenic Escherichia coli); MEFA (multiepitope fusion antigen); Vaccine