Introduction. Francisella tularensis is a gram-negative facultative intracellular pathogen that causes lethaldisease in humans, and is a potential biowarfare agent. Surprisingly little is known about the overall proteinphysiology of this bacterium, and only a handful of potential vaccine candidates are identified at themolecular level. Recent efforts were undertaken to sequence the genomes of the attenuated vaccine strainF. tularensis subsp. holarctica LVS and the virulent F. tularensis subsp. tularensis strain Schu4. Thecompleted genome sequences of these two organisms enable the application of high throughput genomicand proteomic techniques for the identification of vaccine antigens. Specifically, proteomic techniquesincluding array technologies developed implemented to identify dominant antigens of other intracellularpathogens will be applied to F. tularensis. These antigen screens will provide a defined set of potentialvaccine candidates that will be evaluated in conjunction with adjuvant formulations to assess protectiveefficacy and the nature of the immune response elicited. The overall goal of this project is to develop threeto four vaccine formulations that are suitable for scale-up production under GMP and transition to clinicalstudies.Project interactions: This project will be closely integrated with other projects and with Core Facilitiesdescribed in this proposal. The Pis of this project is Dr. Belisle. Dr. Petersen and Bosio will serve as Co-Pis, and Dr. Feigner will serve as the PI of a sub-contract to the University of California, Irvine. We will workclosely with the Genomics/Proteomics Core to apply bioinformatics to the identification of Schu4 ORFs andthe molecular identification of proteins by mass spectrometry. We will also work closely with the AnimalCore in the implementation of the murine model for F. tularensis infection and will transfer protocols forvaccine testing to this core. As successful vaccine candidates and formulations are identified they will betransferred to the PDM Core for production under GMP conditions. The basic approaches implemented inthis project will be applicable to the development of vaccines against other select agents. In particular therewill be close interaction with groups that are targeting the development of vaccines to Coxiella spp (ProjectsII.E.2, II.E.3, and II.E.4.) and the elucidation of the immune response to Burkholderia spp. (Project M.A.4.).There will also be close interaction with Drs. Kedl and Blair (Project II.C.6) on the use of liposomes as avehicle for the delivery of vaccine antigens
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