title: Production of a conjugate vaccine for Salmonella enterica serovar Typhi from Citrobacter Vi.
abstract: A conjugate vaccine for Salmonella enterica serovar Typhi was produced by chemically linking Vi, purified from Citrobacter, to the non-toxic mutant diphtheria toxin CRM(197) via an adipic dihydrazide spacer using N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide coupling chemistry. The polysaccharide purification process was developed based on Vi precipitation from culture supernatant with cetyl trimethylammonium bromide (CTAB), solubilization of the CTA-polysaccharide salt with ethanol followed by exchange of the CTA(+) counter ion with Na(+). The purified Vi polysaccharide was fully O-acetylated and with high purity. The conjugation process was optimized to obtain a scalable process that has been used for GMP production at pilot scale of vaccine currently in clinical trials.
authors.affiliation: Novartis Vaccines Institute for Global Health, Via Fiorentina 1, 53100 Siena, Italy. francesca.micoli@novartis.com
authors.forename: F
authors.initials: F
authors.lastname: Micoli
authors.forename: S
authors.initials: S
authors.lastname: Rondini
authors.forename: I
authors.initials: I
authors.lastname: Pisoni
authors.forename: C
authors.initials: C
authors.lastname: Giannelli
authors.forename: V
authors.initials: V
authors.lastname: Di Cioccio
authors.forename: P
authors.initials: P
authors.lastname: Costantino
authors.forename: A
authors.initials: A
authors.lastname: Saul
authors.forename: L B
authors.initials: LB
authors.lastname: Martin
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002954:Citrobacter / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods; D014436:Typhoid-Paratyphoid Vaccines / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011135:Polysaccharides, Bacterial; D014436:Typhoid-Paratyphoid Vaccines; D018074:Vaccines, Conjugate; C028581:CRM197 (non-toxic variant of diphtheria toxin)