Diagnostic Assays for early Lyme Borreliosis using in-vivo expressed antigens
DESCRIPTION (provided by applicant): Lyme disease, due to infection with the Ixodes tick-transmitted spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States, with over 38,000 confirmed and probable cases reported to the CDC in 2009. Spirochetes first establish infection in the skin and then disseminate to internal organs such as the heart, the joints, and the nervous system where disease can be seen. The infection is most responsive to antibiotics when identified early,but those with disseminated infection or in whom treatment is delayed can experience debilitating disease that can become unresponsive to antibiotics. The timely and accurate diagnosis of Lyme disease is essential for optimizing the response to therapy and for preventing long- term sequelae of the disease. Serologic tests (ELISA and immunoblot) that detect antibodies against B. burgdorferi are currently the most sensitive and widely available laboratory tests for Lyme disease. These tests utilize whole-cell lysates of cultured laboratory strains of B. burgdorferi as a source of antigens, and therefore do not detect antibodies to B. burgdorferi proteins expressed predominantly in vivo. The recommended two-tiered approach in which a positive or equivocal ELISA is confirmed by immunoblot has only ~30% sensitivity in early stages of infection, and specificity is reduced due to cross-reactivity of B. burgdorferi antigens with those of other infectious agents. This Phase I application seeks to improve upon the currently available serologic tests for Lyme disease through the use of in vivo expressed, B. burgdorferi- specific proteins as antigens. We have recently identified a novel panel of B. burgdorferi genes and proteins that are expressed in the first few weeksof B. burgdorferi infection and to which sera from patients with early Lyme disease react on IgG ELISA. We propose to evaluate these candidate antigens in multiplex format assay for their sensitivity and specificity using human sera samples from well-defined cases of Lyme disease, subjects who have had no known exposure to B. burgdorferi, and other infectious and rheumatic diseases. Peptide pin arrays will map the immunodominant epitopes of candidate antigens with Lyme disease sera in an ELISA format for incorporation into a refined multiplex assay. The results of this Phase I study will set the stage for the development of new sensitive and specific serologic tests for Lyme disease that more accurately reflect the B. burgdorferi antigens inciting immune responses in the infected host. PUBLIC HEALTH RELEVANCE: Lyme disease, due to infection with the spirochete Borrelia burgdorferi, can cause a multisystem illness involving the skin, heart, joints and nervous system. Current blood tests for Lyme disease are not as sensitive early in infection when the infection is most responsive to antibiotics. This application will determine whether a new assay for Lyme disease based on a novel panel of proteins expressed by spirochetes when they initially infect theskin accurately detects Lyme disease in its earliest stages.
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L2 DIAGNOSTICS, LLC
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