title: Antigenicity and immunogenicity of phage library-selected peptide mimics of the major surface proteophosphoglycan antigens of Entamoeba histolytica.
abstract: Entamoeba histolytica is the protozoan parasite responsible for intestinal amoebiasis and amoebic liver abscess, which cause significant morbidity and mortality in many countries of the world. Proteophosphoglycans (PPGs, also known as lipophosphoglycans, LPGs, or lipopeptidophosphoglycans, LPPGs) represent dominant surface components of E. histolytica. Passive immunization with a monoclonal antibody (EH5) directed against these components protected SCID mice from amoebic liver abscess, so PPGs might be regarded as vaccine candidates; however, their structure is very complex and only known in part. They are glycosylphosphatidylinositol-linked polypeptides of unknown sequence carrying glycan side-chains linked to serine residues via phosphodiester bonds. In order to identify peptide mimics of the E. histolytica PPG antigens, we screened six different phage-displayed random peptide libraries with the antibody EH5. Various peptide mimics of different length were identified and, in all the peptides, a distinct consensus sequence Gly-Thr-His-Pro-X-Leu could be identified. The phages strongly bound to the antibody, and the natural antigen inhibited binding of the phages to antibody EH5. In addition, several of the phages induced a significant immunoglobulin G response against amoebic antigens in immunized mice.
authors.affiliation: Division of Specific Prophylaxis and Tropical Medicine, Department of Pathophysiology, Vienna, Austria.
authors.forename: Helen
authors.initials: H
authors.lastname: Melzer
authors.forename: Paola
authors.initials: P
authors.lastname: Fortugno
authors.forename: Erfan
authors.initials: E
authors.lastname: Mansouri
authors.forename: Franco
authors.initials: F
authors.lastname: Felici
authors.forename: Alexandra
authors.initials: A
authors.lastname: Marinets
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wiedermann
authors.forename: Herwig
authors.initials: H
authors.lastname: Kollaritsch
authors.forename: Bernd-Ulrich
authors.initials: BU
authors.lastname: Von Specht
authors.forename: Michael
authors.initials: M
authors.lastname: Duchêne
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001667:Binding, Competitive; D004748:Entamoeba histolytica / Q000254:growth & development / Q000276:immunology* / Q000648:ultrastructure; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006028:Glycosphingolipids / Q000276:immunology; D007114:Immunization; D008018:Life Cycle Stages; D051379:Mice; D019151:Peptide Library; D011509:Proteoglycans / Q000737:chemistry / Q000276:immunology*; D020539:Sequence Analysis, Protein
chemical_list: D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000939:Epitopes; D006028:Glycosphingolipids; D019151:Peptide Library; D011509:Proteoglycans; C008290:lipophosphonoglycan