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

  • Simona Rondini Novartis Vaccines Institute for Global Health
  • Francesca Micoli Novartis Vaccines Institute for Global Health
  • Luisa Lanzilao Novartis Vaccines Institute for Global Health
  • Ivan Pisoni Novartis Vaccines Institute for Global Health
  • Vito Di Cioccio Novartis Vaccines Institute for Global Health
  • Allan J Saul Novartis Vaccines Institute for Global Health
  • Laura B Martin Novartis Vaccines Institute for Global Health
Keywords: S. Typhi, Vi, Citrobacter, conjugate vaccine, Vi-CRM197

Abstract

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.

Author Biographies

Simona Rondini, Novartis Vaccines Institute for Global Health
Simona Rondini is currently the project leader of nontyphoidal salmonella glyconjugate vaccine program. She also worked for S. Typhi and Paratyphi A vaccine development at NVGH.
Francesca Micoli, Novartis Vaccines Institute for Global Health
Francesca Micoli is the expert of glycoconjugate chemistry at NVGH
Luisa Lanzilao, Novartis Vaccines Institute for Global Health
Luisa Lanzilao is a lab technician at NVGH
Ivan Pisoni, Novartis Vaccines Institute for Global Health
Ivan Pisoni is an expert in analytical techniques at NVGH
Vito Di Cioccio, Novartis Vaccines Institute for Global Health
Vito Di Cioccio is the head of Technical Department at NVGH
Allan J Saul, Novartis Vaccines Institute for Global Health
Allan J Saul is the CEO of NVGH
Laura B Martin, Novartis Vaccines Institute for Global Health
Laura B. Martin is the head of the projects in Technical Development at NVGH
Published
2012-11-26
How to Cite
1.
Rondini S, Micoli F, Lanzilao L, Pisoni I, Di Cioccio V, Saul AJ, Martin LB (2012) Characterization of Citrobacter sp. line 328 as a source of Vi for a Vi-CRM197 glycoconjugate vaccine against Salmonella Typhi. J Infect Dev Ctries 6:763-773. doi: 10.3855/jidc.2495
Section
Original Articles