title: C-terminal invariable domain of VlsE may not serve as target for protective immune response against Borrelia burgdorferi.
abstract: VlsE, the variable surface antigen of the Lyme disease spirochete, Borrelia burgdorferi, contains two invariable domains, at the amino and carboxyl termini, respectively, which collectively account for approximately one-half of the entire molecule's length and remain unchanged during antigenic variation. It is not known if these two invariable domains are exposed at the surface of either the antigen or the spirochete. If they are exposed at the spirochete's surface, they may elicit a protective immune response against B. burgdorferi and serve as vaccine candidates. In this study, a 51-mer synthetic peptide that reproduced the entire sequence of the C-terminal invariable domain of VlsE was conjugated to the carrier keyhole limpet hemocyanin and used to immunize mice. Generated mouse antibody was able to immunoprecipitate native VlsE extracted from cultured B. burgdorferi B31 spirochetes, indicating that the C-terminal invariable domain was exposed at the antigen's surface. However, this domain was inaccessible to antibody binding at the surface of cultured intact spirochetes, as demonstrated by both an immunofluorescence experiment and an in vitro killing assay. Mouse antibody to the C-terminal invariable domain was not able to confer protection against B. burgdorferi infection, indicating that this domain was unlikely exposed at the spirochete's surface in vivo. We concluded that the C-terminal invariable domain was exposed at the antigen's surface but not at the surface of either cultured or in vivo spirochetes and thus cannot elicit protection against B. burgdorferi infection.
authors.affiliation: Department of Parasitology, Tulane Regional Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana 70433, USA.
authors.forename: F T
authors.initials: FT
authors.lastname: Liang
authors.forename: M B
authors.initials: MB
authors.lastname: Jacobs
authors.forename: M T
authors.initials: MT
authors.lastname: Philipp
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D001426:Bacterial Proteins; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D016056:Immunodominant Epitopes; D008074:Lipoproteins / Q000276:immunology*; D008193:Lyme Disease / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D017434:Protein Structure, Tertiary
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001426:Bacterial Proteins; D016056:Immunodominant Epitopes; D008074:Lipoproteins; D010446:Peptide Fragments; C105546:VlsE protein, Borrelia burgdorferi