A significant public health need exists for a standardized serodiagnostic Lyme disease test that distinguishes infection from false positives due to outer surface protein A (OspA) vaccination. A new enzyme-linked immunosorbent assay (ELISA) will be developed using Borrelia burgdorferi antigen preparations that lack OspA antigen, the primary constituent of the Lyme disease vaccine recently approved by the FDA. Vaccine recipients generate OspA antibodies typically causing seropositive test results whether or not actual infection occurred; conventional Lyme disease ELISAs use whole-cell lysates of B. burgdorferi including expressed OspA. Three different OspA-negative antigen candidate preparations initiated in Phase I using three different approaches -- variant strain selection, plasmid gene disruption, and recombinant antigen expression -- will be evaluated in ELISA formats. Sensitivity and specificity will be determined using serum panels representing early and late stages of Lyme disease, normal human sera, and sera from patients with other infectious or autoimmune diseases. The best performing ELISA will be further developed and evaluated extensively in a commercial reference laboratory setting. We anticipate that as the OspA vaccine becomes widely used, the new OspA-negative ELISA will supplant current ELISAs based on whole-cell lysates of standard B. burgdorferi strains.
This research will lead to a serologic ELISA diagnostic for human Lyme disease for use in commercial reference laboratories.
