title: Characterization of Citrobacter sp. line 328 as a source of Vi for a Vi-CRM(197) glycoconjugate vaccine against Salmonella Typhi.
abstract: BACKGROUND
  Salmonella enterica serovar Typhi is the causative agent of typhoid fever with over 22 million cases and over 200,000 deaths reported annually. A vaccine is much needed for use in young children and the Novartis Vaccines Institute for Global Health (NVGH) is developing a conjugate vaccine which targets S. Typhi Vi capsular polysaccharide.
  
  
  METHODS
  Here we describe a method suitable for industrial scale production of the Vi antigen based on expression by a Citrobacter line. We optimized the production of Vi by selecting a suitable Citrobacter strain (Citrobacter 328) that yields high and stable expression of Vi in chemically defined medium under industrial-scale fermentation conditions.
  
  
  RESULTS
  Vi-CRM197 made using Vi from Citrobacter 328 elicited high anti-Vi antibody levels in mice and rabbits.
  
  
  CONCLUSIONS
  Citrobacter 328 is a suitable strain for production of Vi for conjugate anti-Typhi vaccines. Being a BSL-1 organism, which grows in defined medium and stably produces high yields of Vi, it offers excellent potential for safe production of inexpensive vaccines for populations at risk of typhoid fever.
authors.affiliation: Novartis Vaccines Institute for Global Health. simona.rondini@novartis.com
authors.forename: Simona
authors.initials: S
authors.lastname: Rondini
authors.forename: Francesca
authors.initials: F
authors.lastname: Micoli
authors.forename: Luisa
authors.initials: L
authors.lastname: Lanzilao
authors.forename: Ivan
authors.initials: I
authors.lastname: Pisoni
authors.forename: Vito
authors.initials: V
authors.lastname: Di Cioccio
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Saul
authors.forename: Laura B
authors.initials: LB
authors.lastname: Martin
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D016971:Citrobacter freundii / Q000378:metabolism*; D003470:Culture Media / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005285:Fermentation; D051379:Mice; D016296:Mutagenesis; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis* / Q000378:metabolism; D011817:Rabbits; D022562:Salmonella Vaccines / Q000096:biosynthesis*; D012485:Salmonella typhi / Q000472:pathogenicity; D014435:Typhoid Fever / Q000517:prevention & control; D014436:Typhoid-Paratyphoid Vaccines / Q000096:biosynthesis* / Q000378:metabolism; D018074:Vaccines, Conjugate / Q000096:biosynthesis
chemical_list: D000907:Antibodies, Bacterial; D003470:Culture Media; D011135:Polysaccharides, Bacterial; D022562:Salmonella Vaccines; D014436:Typhoid-Paratyphoid Vaccines; D018074:Vaccines, Conjugate; C057664:Vi polysaccharide vaccine, typhoid; C054154:capsular polysaccharide, Salmonella