The goal of the parent award is epitope discovery and validation, determination of mechanisms of action of antibodies to newly identified epitopes, and deposition on epitopes into the Agency’s Immune Epitope Database (IEDB.org). The Contractor is screening a large collection of serum samples collected from patients diagnosed with Lyme disease, caused by the pathogen, Borrelia burgdorferi, to identify antibodies associated with protection from Lyme disease, as well as antibodies that may induce debilitating, chronic symptoms of Lyme disease. During the course of performing the contracted work, he identified two proteins that induce antibodies found in the sera of patients with symptoms of Lyme arthritis and Lyme neuroborreliosis. These findings have strong relevance to our understanding of the pathology of chronic Lyme disease symptoms and may inform vaccine development. Rational design of Lyme subunit vaccines will need to include epitopes that prevent Borrelia infection but should also exclude regions that may cause adverse side effects through induction of pathogenic antibody responses. There is currently no vaccine approved for humans. The tick population continues to rise with a corresponding increase in the incidences of tickborne disease in humans. The ability to address this growing public health concern depends on research on understanding human responses to infection and using the data as clues for identification of protective components for testing as vaccine candidates.