Proteins normally found on the surface of the Lyme disease spirochete, Borrelia burgdorferi, affect the antigenicity, immunological reactivity and host cell interaction of the spirochete. These proteins are the major focus of current efforts to develop safe, effective vaccines to prevent Lyme disease. The overall efficacy of a recombinant vaccine will depend upon the selection of one or more immunoprotective target(s). Genetic variation, particularly the heterogeneity of surface proteins, can alter the antigenicity of the immunoprotective epitopes of the target proteins. Rational development of effective vaccines, therefore, requires determination of the sequence variation of the major outer surface proteins in B. burgdorferi and integration of this knowledge with the tertiary structure of these proteins to help define those regions where changes will influence interaction with antibodies. In order to provide a starting point to elucidate the molecular details of the interactions of the Borrelia surface proteins with the immune system we-. are attempting to use crystallographic techniques to solve the structures of Borrelia's major outer surface proteins alone and in complexes with Fab fragments of protective monoclonal antibodies. Experiments are also described aimed at development of multipeptide chimers to expand the immunoprotective potential of a given vaccine candidate. In particular, we shall -determine the location of protective epitopes within the outer surface proteins and then use these regions to construct multipeptide recombinant hybrids that would extend immunization simultaneously to more than one genospecies and therefore have broad applic ions- in prevention and diagnosis of Lyme disease.
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