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Vi-CRM 197 as a new conjugate vaccine against Salmonella Typhi
F Micoli1, S Rondini, I Pisoni
1Novartis Vaccines Institute for Global Health, Via Fiorentina 1, 53100 Siena, Italy. francesca.micoli@novartis.com
Insights
Developing a typhoid conjugate vaccine using Vi-CRM(197) offers a low-cost, effective solution, particularly for children in developing nations. This approach utilizes a safe carrier protein for broad applicability.
Area of Science:
- Vaccinology
- Microbial pathogenesis
- Bioconjugation chemistry
Background:
- Typhoid fever remains a significant public health concern, especially in developing countries, necessitating effective and affordable vaccines.
- The capsular polysaccharide (Vi) of Salmonella Typhi is a key virulence factor and a target for vaccine development.
- Previous conjugate vaccines (Vi-rEPA) have demonstrated high efficacy, but alternative carrier proteins are explored for improved production and cost-effectiveness.
Purpose of the Study:
- To investigate the development of a typhoid conjugate vaccine using alternative carrier proteins suitable for large-scale production.
- To standardize the conjugation process and establish assays for routine lot release.
- To evaluate the immunogenicity of a novel typhoid conjugate vaccine candidate.
Main Methods:
- Utilized Vi from Citrobacter freundii (a BSL1 organism) as an alternative source.
- Conjugated Vi to CRM197, a non-toxic diphtheria toxin mutant widely used in infant vaccines.
- Standardized conjugation procedures and developed lot release assays for scalability.
Main Results:
- High yields of Vi-CRM197 conjugate were achieved.
- Vi-CRM197 demonstrated significant immunogenicity in animal models, even without adjuvants.
- The conjugation process and assays were optimized for production scale.
Conclusions:
- Vi-CRM197 is a promising candidate for a commercially viable and effective typhoid conjugate vaccine.
- This vaccine strategy holds potential for reducing the burden of typhoid fever in developing countries.
- The use of CRM197 as a carrier protein facilitates integration into existing infant vaccination schedules.
Abstract:
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.
