Plague Vaccine: Identifying Immunogenic Yersinia Pestis Surface Proteins that are Expressed

A. Specific Aims Yersinia pestis is a highly virulent extracellular pathogen that poses a devastating threat as a bioterrorism agent. Untreated, pneumonic plague is 100% fatal in as few as two days. No vaccine is available for plague. Vaccines under development contain the antigens LcrV and Fl. They provide modest protection against pneumonic plague but only if the infecting strain expresses the FI capsular protein. To find alternative vaccine candidates, we will use proteomics for identification of Y. pestis surface proteins that are expressed during pneumonic plague. These proteins offer potential targets for opsonization and blocking reagents and will be prioritized by their relative abundance, genetic upregulation during a pneumonic infection, recognition by human plague convalescent serum, and indications of potential virulence function. By using a multitiered approach (Aims I & 2), we hope identify potential vaccine candidates that will protect against both encapsulated and non-encapsulated Y. pestis. These antigens may also prove useful for the production of immunoglobulin that may be used for passive immunization of exposed persons. Our findings will enhance our arsenal of protection against bioterroristic use of Y.pestis and will improve our understanding of the pathogenesis of pneumonic plague. Our aims are: 1. Use a bioinformatics-informed approach to identify immunogenic surface proteins with potential roles in the pathogenesis of pneumonic plague. 2. Use a novel "anchored" RT-PCR technique to determine if expression of the genes identified in Aim 1 are upregulated during pneumonic plague.