Antigenic Conservation of an Immunodominant Invariable Region of the VlsE Lipoprotein among European Pathogenic Genospecies ofBorrelia burgdorferiSL

Abstract

Lyme disease is caused by genetically divergent spirochetes, including 3 pathogenic genospecies: Borrelia burgdorferi sensu stricto, B. garinii, and B. afzelii. Serodiagnosis is complicated by this genetic diversity. A synthetic peptide (C(6)), based on the 26-mer invariable region (IR(6)) of the variable surface antigen of B. burgdorferi (VlsE), was used as ELISA antigen, to test serum samples collected from mice experimentally infected with the 3 genospecies and from European patients with Lyme disease. Regardless of the infecting strains, mice produced a strong antibody response to C(6), which indicates that IR(6) is antigenically conserved among the pathogenic genospecies. Twenty of 23 patients with culture-confirmed erythema migrans had a detectable antibody response to C(6). A sensitivity of 95.2% was achieved, with serum samples collected from patients with well-defined acrodermatitis chronica atrophicans. Fourteen of 20 patients with symptoms of late Lyme disease also had a positive anti-IR(6) ELISA. Thus, it is possible that C(6) may be used to serodiagnose Lyme disease universally.

Dogs Vaccinated with Common Lyme Disease Vaccines Do Not Respond to IR6, the Conserved Immunodominant Region of the VlsE Surface Protein ofBorrelia burgdorferi

“…The design of the experiments whose results are reported herein was aimed at offering conclusive evidence that C 6 -based immunoenzyme assays, already shown to be sensitive and specific (11,14,15), did not react with serum antibodies from vaccinated dogs that were known to be free of a B. burgdorferi infection. The results obtained amply demonstrate the absence of such cross-reactivity in the face of vaccine antibody titers, as measured by IFA, that are probably higher than titers obtained with a regular two-dose vaccine administration regimen.…”

“…Serodiagnosis with the C 6 peptide has been found to be highly specific (11,14,15). Except for sequences present in the vlsE gene and vls loci of B. burgdorferi, no other sequences homologous to C 6 could be identified by the BLAST search algorithm in the National Center for Biotechnology Information protein sequence database (15).…”

“…Recently, a short segment of a B. burgdorferi surface protein named VlsE (Vmp-like sequence, expressed) has been used (9)(10)(11)(12)(13)(14)(15)(16), in addition to the full-length protein (7), to construct antibody detection assays that have excellent sensitivity and virtually eliminate false-positive results. This peptide, named C 6 , is 25 amino acids in length and reproduces the sequence of an immunodominant and conserved region (IR 6 ) of VlsE (12).…”

Lyme borreliosis

“…20 The variable major protein-like sequence expressed (VlsE) Osp has an invariable region conserved across many species of Borrelia and is highly immunogenic in mice, dogs, and primates. [21][22][23][24] An understanding of the kinetics of these and other expressed proteins (eg, decorin binding proteins and flagellin) is important for diagnosis (measurement of mammalian antibody response to bacterial proteins) and prevention (identification of potential vaccine candidates) of Lyme borreliosis.…”

C6 Peptides fromBorrelia BurgdorferiSensu Stricto,Borrelia AfzeliiandBorrelia Gariniias Antigens for Serological Diagnosis of Lyme Borreliosis

“…eliSA tests using various B. burgdorferi sensu lato protein antigens have been described (ospA, ospc, Fla, Vlse). Among them, Vlse is the most sensitive diagnostic antigen with conserved immunogenic epitopes (4).…”