New Vaccine Candidate for Pneumonic Plague

This project proposes to identify large (> 50 kDa) surface proteins that are expressed during lung infection by the plague bacterium Yersinia pestis. These will be prioritized by conditions for expression, relative abundance, recognition by plague convalescent serum, and indications from homology with the databases of potential virulence function. Ten of these will be characterized for their necessity for virulence in a mouse model of pneumonic plague. Four will then be chosen for detailed studies of immunogenicity. It is hoped that one or more of these will prove to be protective against pneumonic plague caused by a non-encapsulated strain against which vaccines currently in development will not protect adequately. Such vaccine candidates also can in the future serve as the basis for a protective immune globulin reagent for rapid protection of potentially exposed people; and a strong, specific antibody reagent might contribute to an improved multiplex detection method. Our findings will enhance our arsenal of means to protect against potential bioterrorism use of Yersinia pestis and also will improve our understanding of the pathogenesis of pneumonic plague. Our aims are: Aim 1. Identification of large surface proteins expressed in the mouse lung after aerosol challenge. Aim 2. Characterization and sorting of surface proteins. Aim 3. Immunization studies. We have changed Aim 3 from "Vaccination studies" to "Immunization studies". Given the late arrival of funds and shortened first year of support, we are not confident that we can accomplish protection studies that would come after the planned immunization studies.