Vi-CRM 197 as a new conjugate vaccine against Salmonella Typhi.
An efficacious, low cost vaccine against typhoid fever, especially for young children, would make a major impact on disease burden in developing countries. The virulence capsular polysaccharide of Salmonella Typhi (Vi) coupled to recombinant mutant Pseudomonas aeruginosa exoprotein A (Vi-rEPA) has been shown to be highly efficacious. We investigated the use of carrier proteins included in infant vaccines, standardized the conjugation process and developed key assays required for routine lot release at production scale. Vi from a BSL1 organism, Citrobacter freundii, strain WR7011, was used as an alternative to Vi from S. Typhi. We showed that Vi conjugated to CRM(197), a non-toxic mutant of diphtheria toxin, widely used in commercial vaccines, was produced at high yield. Vi-CRM(197) proved immunogenic in animal studies, even without adjuvant. Thus, Vi-CRM(197) appears to be a suitable candidate for the development of a commercially viable, effective typhoid vaccine for developing countries.
Novartis Vaccines Institute for Global Health, Via Fiorentina 1, 53100 Siena, Italy. francesca.micoli@novartis.com
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F
Micoli
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S
Rondini
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I
Pisoni
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D
Proietti
F
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Berti
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Costantino
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R
Rappuoli
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Szu
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Saul
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Martin
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000008:administration & dosage*; D016971:Citrobacter freundii / Q000737:chemistry / Q000276:immunology; D005260:Female; D007117:Immunization, Secondary / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D012290:Rickettsial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012485:Salmonella typhi / Q000737:chemistry / Q000276:immunology; D014435:Typhoid Fever / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D011135:Polysaccharides, Bacterial; D012290:Rickettsial Vaccines; D018074:Vaccines, Conjugate; C028280:typhus vaccine; C028581:CRM197 (non-toxic variant of diphtheria toxin)