Abstract – Fiscal Year 2003

Abstract: With the killed whole-cell plague vaccine no longer being manufactured, recombinant subunit vaccines are currently being sought. The goal of this project is to establish whether proteins associated with a recently described chromosomal type III secretion system (cTTSS), common to Yersinia pestis and Y. pseudotuberculosis, could provide new potential candidate antigens for use in a multivalent plague vaccine. The role of this new cTTSS, first described upon release of the Y. pestis genome sequence, has yet to be determined; however, it may be required for intracellular survival and bacterial replication within macrophages and epithelial cells. Based upon the high degree of sequence similarity this cTTSS shares with a TTSS contained within the Salmonella Pathogenicity Island 2 (SPI-2). In Salmonella, SPI-2 has been shown to be not only essential for bacterial survival and replication in macrophages, but is also required for dissemination and systemic infection. The specific aims of this project are to: 1) generate isogenic Yersinia strains defective in various components of the cTTSS and examine these mutants for their capacity to survive and replicate in macrophage cell lines as well as assess their lethality in mouse challenge studies, and 2) identify the environmental conditions under which this cTTSS is induced and the effector molecules that are secreted by this system. If the Yersinia cTTSS is found to be required for virulence, then components of this system and its associated effector molecules will be further characterized to determine whether these new target antigens are applicable in a subunit vaccine.

Institution: Food and Drug Administration

Date: July 2003

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Last updated: July 16, 2003

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