Research Project
7326480
[unreadable] DESCRIPTION (provided by applicant): Lyme disease (LD), the most commonly reported arthropod-borne infection in the United States and Europe, is increasing in its distribution on both continents. The commercial failure of the LD vaccine in the U.S. means that timely detection and treatment of cases is still a mainstay for preventing human morbidity. While an assay of sera for antibodies to the LD organism, Borrelia burgdorferi, remains the most common method for laboratory support of the diagnosis of LD, there have been few if any improvements in the performance of these serological laboratory assays for two decades. The premise of this proposal is that an array of recombinant proteins that represent most of the genes of B. burgdorferi can be used to identify new or hitherto overlooked antigens of high diagnostic value. The application further proposes that a set of these candidate antigens will provide for antibody assays with higher sensitivity and specificity than currently available assays. Substantial preliminary data, including the production of a first generation B. burgdorferi array and its study with sera, show the feasibility of the proposed research and the likelihood of success of this one-year Phase 1 project. The specific aims of the proposal are the following: (1) Achieve =90% representation of B. burgdorferi genes as proteins in the arrays and fabricate the arrays on chips for subsequent experiments. For this aim selected proteins of two LD agents in Europe and Asia, B. garinii and B. afzelii, will also be applied to chips. (2) Evaluate the antibody responses to proteins in the array using well-characterized sera from patients with documented LD at various stages of infection and from controls. Statistical and bioinformatics analyses of antibody binding in these large data sets will be used identify candidate antigens. (3) From among these candidates, select 5-10 antigens that show the most promise for further development as components for subunit diagnostic assays, initially in test platforms that are widely accepted and implemented, such as an adaptation of a Western blot assay. [unreadable] [unreadable] Lyme disease (LD), the most commonly reported arthropod-borne infection in the United States and Europe, is increasing in its distribution on both continents. The commercial failure of the LD vaccine in the U.S. means that timely detection and treatment of cases is still a mainstay for preventing human morbidity. There have been few if any improvements in the performance of these serological laboratory assays for two decades. The premise of this proposal is that an array of recombinant proteins that represent most of the genes of B. burgdorferi can be used to identify new or hitherto overlooked antigens of high diagnostic value. The application further proposes that a set of these candidate antigens will provide for antibody assays with higher sensitivity and specificity than currently available assays. [unreadable] [unreadable] [unreadable]
