Low Infectious Dose Entropathogens: Detection, Pathogenesis and VaccinologyResearch Project V includes three Sub-Projects focused on key new aspects of the genomics,pathogenesis and vaccinology of the three leading Category B low-dose enteropathogens, and on theirdetection in clinical and environmental samples. These include the highly chlorine-resistant Cryptosporidiumparvum, the most fearsome Shigella threat (S. dysenteriae 1) and the largely untreatable, Shiga toxinproducingenterohemorrhagic E. coil These three pathogens all pose serious risks as low infectious doseagents of bioterrorism as well as major national and global health endemic and epidemic challenges. Theteam of investigators for this project has a very strong track record of working with these organisms. Led byexperienced investigators with international reputations in enteric diseases, Richard L. Guerrant and JamesB. Kaper, this project builds upon highly productive expertise and upon longstanding and new crossinstitutionalsynergies at UVa, UMd, VCU, VT, USUHS, UVt, and JHU.Our first Sub-Project V.1, on 'Cryptosporidium genomics, pathogenesis and vaccinology' buildsupon the near complete sequencing of the human (type 1) C. parvum genome by the VCU group, thepublished tissue culture, animal and field experience with Cryptosporidium by the UVa group, the plantbasedproduction of mucosal vaccines at VT and on studies of the genetics of susceptibility at UVa, UVt,and JHU to identify and express type 1 (human) C. parvum candidate genes, define their roles inpathogenesis and immunity, express promising candidates and define genetic determinants of humansusceptibility and thus optimal approaches to vaccine development. Sub-Project V.2 will engage UMd,USUHS and UVa colleagues to construct novel Shigella dysenteriae and enterohemorrhagic E. coli (EHEC)vaccines and develop novel therapeutics for EHEC disease. Sub-Project V.3 will produce additionaldiagnostic 'deliverables' for detection of human fecal contamination of water (and possibly food) as well asthe specific detection of the three low infectious dose category B enteropathogens on which our RCEEnterics Program is focused, C. parvum, S. dysenteriae and EHEC.
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