Characterization of Citrobacter sp. line 328 as a source of Vi for a Vi-CRM197 glycoconjugate vaccine against Salmonella Typhi

Introduction: 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 v...

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Main Authors: Simona Rondini, Francesca Micoli, Luisa Lanzilao, Ivan Pisoni, Vito Di Cioccio, Allan J Saul, Laura B Martin
Format: Article
Language:English
Published: The Journal of Infection in Developing Countries 2012-11-01
Series:Journal of Infection in Developing Countries
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Online Access:https://jidc.org/index.php/journal/article/view/2495
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Summary:Introduction: 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. Methodology: 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.
ISSN:1972-2680