Lyme disease is a zoonotic disease that is transmitted to humans through the bite of infected Ixodes ticks. Lyme disease now represents the most common arthropod borne disease in N. America. Three species of Borrelia are known to cause Lyme disease in humans; B. burgdorferi, B. garinii and B. afzelii. Infection with these bacteria is chronic and can persist for several years. At the present time there is no commercially available Lyme disease vaccine. As a result there is a significant and serious void in the available preventive strategies for Lyme disease. We have recently characterized two proteins that offer great promise for vaccine development. These proteins, FHBP25 and FHBP27 (FHBP25/27), play a pivotal role in Lyme disease pathogenesis by promoting immune evasion through the binding of the complement regulatory protein factor H. Factor H bound to the spirochetal cell surface interacts with factor I which can then cleave the critical complement component, C3b. This decreases the efficiency of the alternate complement cascade, which in turn facilitates the establishment of chronic infection. It is our hypothesis that an FBHP25/27 based vaccine would be superior to other potential vaccines in several regards. First vaccination with FHBP25/27 will result in the production of bactericidal Ab. Second, vaccination will elicit the production of antibodies that would block the ability of FHBP25/27 to bind factor H and thereby render the spirochetes highly susceptible to opsonization and phagocytosis. Lastly, this vaccine has the potential to mediate spirochetes killing in both the tick and mammalian environments. The goal of this application is to determine the efficacy of an FHBP25/27 vaccine and determine its correlates of protection.
| McDowell, John V; Harlin, Matthew E; Rogers, Elizabeth A et al. (2005) Putative coiled-coil structural elements of the BBA68 protein of Lyme disease spirochetes are required for formation of its factor H binding site. J Bacteriol 187:1317-23 |
| McDowell, John V; Wolfgang, Jill; Senty, Lauren et al. (2004) Demonstration of the involvement of outer surface protein E coiled coil structural domains and higher order structural elements in the binding of infection-induced antibody and the complement-regulatory protein, factor H. J Immunol 173:7471-80 |
