BIOPEPTIDES CORP — Department of Health and Human Services SBIR Phase II: NIAID

Description

Project Summary Lyme disease is a progressive disease that in later stages can lead to debilitating permanent damage to the nervous and musculoskeletal systems Early treatment with an appropriate course of antibiotics is highly effective at clearing infection and preventing disease progression Therefore early diagnosis is critical for ensuring patient outcome However most current IgM and IgG serological assays are not sensitive enough to detect disease at the time most patients seek medical attention More effective alternatives are necessary A T cell based cytokine release assay offers a unique and innovative alternative to serological assays Unlike antibody responses which may remain elevated for years after pathogen clearance the T cell response rapidly wanes with the cessation of effector function and a collapse in T cell numbers Thus monitoring the T cell activity may provide a more sensitive measure of active disease and pathogen clearance than serum antibody responses In phase I we identified unique peptides derived from several antigens expressed by Borrelia burgdorferi during the course of human disease Using a mixture of peptides from four of these antigens we generated a prototype assay that induced detectable secretion of IFN following overnight stimulation of whole blood obtained from patients with well characterized early Lyme disease and observed that IFN secretion was significantly decreased in the same patients days after antibiotic therapy indicating successful clearance of the bacteria These data demonstrate concrete proof of principle that a cytokine release assay for the diagnosis of early Lyme disease can be created and can be successful In this phase II application we will optimize this assay by selecting additional peptide epitopes that stimulate release of IFN from T cells activated in response to infection with Borrelia spp confirming specificity by evaluating samples from patients with potential cross reactive illnesses and evaluating the performance of a QuantiFERON like test before and after treatment of all stages of Lyme disease This will result in the creation of a finalized cytokine release assay for Lyme disease for FDA submission Project Narrative Lyme disease is a progressive disease that can result in debilitating permanent damage to the nervous and musculoskeletal systems if appropriate treatment is not administered at the early stage Unfortunately current laboratory tests for Lyme disease are not very sensitive during early disease and cannot determine if antibiotic treatment was effective We are developing an innovative diagnostic assay that measures the response of T lymphocytes specific for the bacteria that causes Lyme disease Borrelia burgdorferi rather than measuring antibody levels This test is both highly sensitive and highly specific for the detection of disease and can also distinguish between individuals that currently have Lyme disease vs those that had it previously and can determine if treatment was successful