title: Development of lipopolysaccharide-mimicking peptides and their immunoprotectivity against Vibrio cholerae serogroup O1.
abstract: Vibrio cholerae serogroup O1 is the main causative agent of cholera diseases defined by life threatening rice watery diarrhea. Cholera routine vaccination has failed in controlling epidemics in developing countries because of their hard and expensive production. In this study, our aim was to investigate phage displayed mimotopes that could mimic V. cholerae lipopolysaccharide (LPS). Although LPS of Vibrio, as an endotoxin, can stimulate the immune system, thereby making it a suitable candidate for cholera vaccine, its toxicity remains as a main problem. Phage particles displaying 12 amino acid peptides were selected from phage library mimicking the antigenic epitopes of LPS from vibrio. The screening was carried out using single-domain antibody fragment VHH against LPS as target through three rounds of selection. Three clones with highest affinity to VHH were selected. To find out a new and efficient vaccine against cholera, these three phage particles containing high-affinity peptides were administered to mice to investigate the active and passive immunity. Out of 20 particles, three showed the highest affinity toward VHH. ELISA was carried out with immunized mice sera using LPS and three selected phages particles individually. ETEC, Shigella sonnei, and clinical isolates were used as bacterial targets. These three selected phages (individually or in combination) could stimulate mice immune system producing active and passive immunity. The mice immunized with phage particles could protect about 14 LD50 of V. cholerae. In conclusion, these peptides are mimicking LPS and can potentially act as vaccine candidates against V. cholerae. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: Department of Biology, Shahed University, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mohammad Pour Ghazi
authors.affiliation: Department of Biology, Shahed University, Tehran, Iran.
authors.forename: Seyed Latif Mousavi
authors.identifier: http://orcid.org/0000-0002-4635-8716
authors.initials: SL
authors.lastname: Gargari
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000276:immunology; D000915:Antibody Affinity; D002771:Cholera / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D007114:Immunization; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D019151:Peptide Library; D057786:Peptidomimetics / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology; D061905:Single-Domain Antibodies / Q000096:biosynthesis* / Q000276:immunology; D016896:Treatment Outcome; D041241:Vibrio cholerae O1 / Q000737:chemistry / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity; D014771:Virion / Q000737:chemistry / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D022121:Cholera Vaccines; D000939:Epitopes; D008070:Lipopolysaccharides; D019151:Peptide Library; D057786:Peptidomimetics; D061905:Single-Domain Antibodies
keywords: VHH; lipopolysaccharides; mimicking peptides; phage display; protectivity; vaccine