Immunization with either Borrelia burgdorferi outer surface protein (Osp) A or OspC induces protective immunity to subsequent challenge with the strain of B. burgdorferi from which the Osp's were derived. However, OspA and OspC are heterogeneous and protection against one strain does not necessarily protect against challenge with other strains. The investigators propose to develop a polyvalent vaccine with a board range of protection. In preliminary studies, the investigators have constructed chimeric genes that express proteins comprised of OspA and OspC segments from selected strains of Borrelia. These chimeric genes will be overexpressed in E. coli as unlipidated protein chimers. Unlipidated proteins can be produced at much higher concentrations than lipidated proteins. The side-chains of Cys residues in these recombinant chimers will be chemically modified to introduce lipid membrane anchors. During Phase II, the synthetic lipoprotein chimers will be tested in animal models, separately and in combination, to assess their efficacy in preventing infection with an array of Borrelia strains. The investigators expect that this will produce a second generation human vaccine that will provide a longer duration of immune protection compared to vaccine candidates currently in clinical trials.
Thesaurus Terms:Borrelia, Lyme disease, biotechnology, vaccine development, vector vaccine bacteria infection mechanism, chimeric protein, gene expression, genetic strain, lipid, protein structure Escherichia coli
