Borrelia burgdorferi is the causative agent of Lyme borreliosis in humans. In the Midwestern and Northeastern regions of the United States, B. burgdorferi is maintained in nature by an enzootic cycle between Ixodes sp. ticks and small mammals such as Peromyscus leucopus. B. burgdorferi, a mostly clonal species, displays abundant genetic diversity in the loci encoding a highly immunodominant protein, the outer surface protein C (OspC). Studies suggest that this diversity is maintained by balancing selection at the ospC locus, and this selection may be created by the vertebrate host immune response to OspC. However, the current research on this issue has left the extent of antibody cross-reactivity between OspC types mostly unexplored, particularly in the natural host species, P. leucopus.

The working model for the proposed study is that the extensive polymorphism in the ospC loci of different strains of B. burgdorferi is largely a consequence of balancing selection; and that a major, if not sole, determinant of this selection is the immune response by reservoir hosts to the expressed OspC. This model was evaluated by characterizing antibody responses against OspC in several B. burgdorferi-infected host species, particularly in P. leucopus. A protein microarray displaying all OspC types currently known in the United States was produced and used to examine the antibody response to OspC and other more conserved proteins in B. burgdorferi-infected P. leucopus mice, dogs and humans. The main findings of this work were: (i) P. leucopus produce both cross-reactive and type-specific antibodies to OspC proteins; (ii) the genetic diversity amongst B. burgdorferi isolates extends to two new antigenic proteins, BBK07 and BBK12, and the antibody response of P. leucopus reflect these differences; (iii) humans also produce cross-reactive antibodies to OspC, and a region of the OspC molecule likely responsible for this was identified; (iv) infected canines react to many proteins of B. burgdorferi, amongst them OspC, BBK07, BBK12 and newly identified antigens for dogs, BB0844 and BBB14. Collectively, these studies assessed the degree of cross-reactivity between OspC proteins in different mammalian hosts, and other important aspects of the pathobiology of B. burgdorferi.