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Evaluation of the Immunogenicity and Biological Activity of the Citrobacter freundii Vi-CRM197 Conjugate as a Vaccine for Salmonella enterica Serovar Typhi

Rondini, Simona and Micoli, Francesca and Lanzilao, Luisa and Hale, Christine and Saul, Allan and Martin, Laura (2011) Evaluation of the Immunogenicity and Biological Activity of the Citrobacter freundii Vi-CRM197 Conjugate as a Vaccine for Salmonella enterica Serovar Typhi. CLINICAL AND VACCINE IMMUNOLOGY, 18 (3). pp. 460-468. ISSN 1556-6811

Abstract

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-CRM197, where Vi was obtained from Citrobacter freundii WR7011 and
CRM197, 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-CRM197 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.

Item Type: Article
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Keywords: Vi Salmonella Typhi
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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/4700

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