According to the WHO, typhoid fever remains a serious public health problem throughout the world, with an estimated 16-33 million cases and 500,000 to 600,000 deaths annually. The Vi capsule of S. typhi, the causative agent of typhoid fever, is a surface-bound carbohydrate polymer targeted by antibodies to protect against typhoid fever. Purification of this polymer from virulent S. typhi strains poses a danger to those handling the live organism.
Available to license through FDA, a unique strain of Citrobacter freundii, WR7004, was mutated by FDA inventors to create the strain (WR7011) that expresses Vi polysaccharide on its surface. C. freundii WR7011 expresses several times as much Vi polysaccharide as native strains of S. typhi, is nonpathogenic, and is much safer to work with for Vi production or as a vaccine strain. The strain specifically was mutated using nitrosoguanidine. This strain of C. freundii can reduce the cost of purifying the Vi polysaccharide and provide a safe method of manufacturing the polysaccharide.
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Inventors: Dennis Kopecko, De Qi Xu
- Snellings, N.J. et al. Genetic regulation of variable Vi antigen expression in a strain of Citrobacter freundii. J Bacteriol. 1981 Feb;145(2):1010-1017. PMID: 6161917
- Houng, H.S., et al. Expression of Vi antigen in Escherichia coli K-12: characterization of ViaB from Citrobacter freundii and identity of ViaA with RcsB. J Bacteriol. 1992 Sep;174(18):5910-5915. PMID: 1522067
- Ou, J.T., et al. Specific insertion and deletion of insertion sequence 1-like DNA element causes the reversible expression of the virulent capsular antigen Vi of Citrobacter freundii in Escherichia coli. Proc Natl Sci USA. 1988 June;85(12):4402-4405. PMID: 2837765
- Szu, S.C., et al. Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever. J Exp Med. 1987 Nov 1;166(5):1510-24. PMID: 3681191
- Research Tool – no patent protection was pursued for this technology
Product Area: typhoid fever, vaccine, conjugated vaccine, polysaccharide
FDA Reference No: E-2007-001
Ken Millburne, J.D.
FDA Technology Transfer Program