Evaluation of the immunogenicity and biological activity of the Citrobacter freundii Vi-CRM197 conjugate as a vaccine for Salmonella enterica serovar Typhi.
Typhoid fever remains a major health problem in developing countries. Young children are at high risk, and a vaccine effective for this age group is urgently needed. Purified capsular polysaccharide from Salmonella enterica serovar Typhi (Vi) is licensed as a vaccine, providing 50 to 70% protection in individuals older than 5 years. However, this vaccine is ineffective in infants. Vi conjugated to a carrier protein (i.e., an exoprotein A mutant from Pseudomonas aeruginosa [rEPA]) is highly immunogenic, provides long-term protection, and shows more than 90% protective efficacy in children 2 to 5 years old. Here, we describe an alternative glycoconjugate vaccine for S. Typhi, Vi-CRM(197), where Vi was obtained from Citrobacter freundii WR7011 and CRM(197), the mutant diphtheria toxin protein, was used as the carrier. We investigated the optimization of growth conditions for Vi production from C. freundii WR7011 and the immunogenicity of Vi-CRM(197) conjugates in mice. The optimal saccharide/protein ratio of the glycoconjugates was identified for the best antibody production. We also demonstrated the ability of this new vaccine to protect mice against challenge with Vi-positive Salmonella enterica serovar Typhimurium.
Novartis Vaccines Institute for Global Health, Via Fiorentina 1, 53100 Siena, Italy. simona.rondini@novartis.com
Simona
S
Rondini
Francesca
F
Micoli
Luisa
L
Lanzilao
Christine
C
Hale
Allan J
AJ
Saul
Laura B
LB
Martin
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000737:chemistry; D016971:Citrobacter freundii / Q000737:chemistry*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification*; D012481:Salmonella Infections, Animal / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000276:immunology / Q000472:pathogenicity; D014436:Typhoid-Paratyphoid Vaccines / Q000737:chemistry / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D011135:Polysaccharides, Bacterial; D014436:Typhoid-Paratyphoid Vaccines; D018074:Vaccines, Conjugate; C028581:CRM197 (non-toxic variant of diphtheria toxin)
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