Lyme Disease (LD) continues to be a serious health problem in the USA. The chronic nature of the infection can lead to debilitating and serious clinical manifestations. While early diagnosis of LD is the key to successful treatment, accurate diagnosis continues to be a significant problem. In addition, while a vaccine has been developed and licensed there are concerns about the duration of protection it affords and about possible autoimmune responses (IR) in certain genetic backgrounds. These concerns highlight the need for a better understanding of the genetic and antigenic properties of this organism and the molecular mechanisms associated with chronic infection. Our studies on chronic infection and immune evasion by B. burgdorferi (Bb) have focused on a diverse group of plasmid-carried genes and operons that are 5'-flanked by a common upstream promoter-carrying sequence that we call the upstream homology box or UHB element. UHB-flanked genes are organized into 3 distinct gene families: the ospE family, the ospF family, and family 163 (a TIGR designation). The data described below demonstrate that the ospE gene family undergoes mutational and recombinational changes during infection. In addition, members of the ospF gene family are temporally expressed during infection. These different processes culminate in the presentation of new antigenic variants of OspE and OspF on the cell surface that can contribute to immune evasion. Little is known about the role of other UHB-flanked gene families in chronic infection and immune evasion. However, the polymorphic nature of these genes suggests that their organization has been influenced by recent molecular events that may include recombination and rearrangement. The major hypotheses of this proposal are that the OspE, OspF and family 163 proteins contribute to immune evasion in LD and play stage specific roles during infection. The analyses described within will also test the utility of these proteins in vaccine development.
