Lyme disease (LD) is the most common vector-borne illness in the United States and represents aconsiderable diagnostic challenge. 1-3 The current benchmark for LD diagnosis is the standard two-tiered test(STTT), although the modified two-tier test (MTTT) is rapidly becoming an acceptable alternative. 6 Theseassays are highly specific but have poor sensitivity, especially early in the infection. 6, 7Traditional testing is limited by each patient's heterogenous immune response to Borrelia burgdorferi (Bb)antigens. While the paired ELISAs of the MTTT are sensitive and simple to perform, some patients respondweakly to screening reagents. The STTT addresses variation in humoral response by combining an initialELISA with a confirmatory IgG/IgM Western Blot (WB), yet WB sensitivity is modest against any single antigen.This is especially true with IgM results, which also lack the specificity enhancement associated with classswitching. 8 Given these limitations, the ideal serologic assay will combine features of ELISA and WB, but willprovide quantitative and specific results against all major LD antigens. Using current technologies, thisapproach is cost prohibitive.Ciencia Inc. has developed a low-cost, highly-sensitive, fluorescence-based assay platform that supportsexactly this type of quantitative multi-antigen serologic Lyme assay. 4, 9, 10 Dr. Cady at SUNY Poly has used ourgrating-coupled fluorescent plasmonics (GC-FP) assay platform to define antibody responses against a suite ofBb antigens. This preliminary work demonstrates superior sensitivity/specificity compared to STTT (90%/100%vs 60%/100%; n=34 validated samples) and an earlier time to result. Our approach offers a linear responseacross the full dynamic range, a rapid time to result, low reagent costs. Antigen spots may be added for anegligible cost, so a broader tickborne disease (TBD) panels could be performed for the price of one ELISA.With this Phase I STTR, Ciencia will partner with Dr. Cady (SUNY Polytechnic Institute) and Dr. Strle(Wadsworth Center) to build upon our preliminary self-funded exploration of Lyme serodiagnostics. We aim tovalidate our preliminary results using a larger set of well-characterized LD samples and appropriate controlsfrom the CDC and NY State DoH, including an estimate of time to positivity using samples collectedlongitudinally. In parallel, Ciencia aims to improve sample handling and overall ease of use by implementing acartridge-based system and automated processing that will make GC-FP a viable alternative to methods suchas the STTT and MTTT, both of which are cumbersome and time consuming. The ultimate goal is to provide arapid, easy-to-use, and highly accurate test that can be used outside traditional clinical laboratories. Based onthe success of Phase I, the Phase II effort would optimize the test for diagnosis of Lyme disease caused byEuropean Borrelia strains and expand it to other tickborne diseases. Phase II would also permit designrefinements and initiation of the FDA approval process.
Public Health Relevance Statement: Project Narrative Lyme Disease diagnosis is hindered by low titers of clinically relevant antibodies early in infection and complex multi-tier testing protocols. With this project, Ciencia and collaborators respond to the "Notice of Special Interest: Advancing Research for Tickborne Diseases" by further validating our Lyme serodiagnostics assay and by developing an easy-to-use system for sample handling and data interpretation. Through partnership with SUNY Polytechnic Institute and the Wadsworth Center (NY State Dept. of Health), Ciencia aims to develop a next generation assay platform that can bring rapid, low-cost, easy-to-use, and high-quality diagnostics outside traditional testing sites.
Project Terms: <7S Gamma Globulin><19S Gamma Globulin> | | 