Evaluation of the Recombinant VlsE-Based Liaison Chemiluminescence Immunoassay for Detection ofBorrelia burgdorferiand Diagnosis of Lyme Disease

Abstract

Recent efforts to improve the serologic diagnosis of Lyme disease have included the use of a synthetic peptide (C6) that reproduces the sequence of invariable region 6 of VlsE, the variable surface antigen of Borrelia burgdorferi. In the present study, the diagnostic performance of DiaSorin's recombinant VlsE-based chemiluminescence immunoassay in 1,947 human serum samples was evaluated. Sensitivity was determined using two serum panels from the CDC. For panel I, we observed sensitivities of 68.4% and 75.6% for subjects with early, localized (n ‫؍‬ 19) or disseminated (n ‫؍‬ 41) disease, respectively. For panel II, we observed sensitivities of 61.5% and 100% for subjects with early (n ‫؍‬ 26) or late-stage (n ‫؍‬ 11) disease, respectively. We observed a specificity of 99.5% for healthy donors (n ‫؍‬ 600) living either in regions of the United States where the disease is endemic or in regions where it is not endemic. Overall, specificity among 207 potentially cross-reactive sera from subjects who had other spirochetal infections, nonspirochetal infections including bacterial and viral infections, or autoimmune or neurologic disease; who were positive for rheumatoid factor or anti-mouse antibodies; or who had been previously vaccinated for Lyme disease was 93.7%. In a direct comparison of 1,038 prospectively collected samples for Lyme disease testing we observed a relative sensitivity of 70%, a relative specificity of 99.1%, and an overall agreement of 97.1% between the DiaSorin recombinant VlsE chemiluminescence immunoassay and the Immunetics peptide-based C6 enzyme-linked immunosorbent assay.

Humoral Immune Responses in Patients with Lyme Neuroborreliosis

“…These findings are mostly in line with other reports on the presence of borrelial antibodies in the sera of patients with Lyme neuroborreliosis, as determined by assays using the internal fragment of p41 as the antigen (IgM antibodies were detected in 49 to 67.9% of patients with Lyme neuroborreliosis and IgG in 34 to 76.6%) (1, 9) and by tests based on OspC as the antigen (47 to 53% seropositivity for IgM antibodies) (1, 9), but positivity was less than that in assays utilizing the VlsE antigen (73% for IgM and 100% for IgG) (1,11,21).…”

Evaluation of Modified 2-Tiered Serodiagnostic Testing Algorithms for Early Lyme Disease

“…Next-generation first-tier assays have been approved for diagnostic use in the United States [3][4][5][6]. These assays are prepared from recombinant proteins or synthetic peptides that correspond to spirochetal antigens known to induce relatively early and robust humoral immune responses [7].…”

Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease

“…Additional improvements to the current testing algorithm using the VlsE antigen have been proposed (29)(30)(31), as has using peptide subunits from the antigens OspC, OppA, BBK07, and DbpAB to reduce cross-reactive background (32)(33)(34)(35)(36). Different platforms, including luciferase immunoprecipitation systems (LIPS) and immuno-PCR, also demonstrate the potential to upgrade current serological testing, with the latter employing recombinant antigens (37)(38)(39).…”