Frontiers in immunology · 2026
Preclinical evaluation of a bivalent conjugate vaccine against Salmonella Typhi and Paratyphi A.
СтатьяНазвание и аннотация: Перевод в очереди
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Alfini Renzo, Di Benedetto Roberta, Carducci Martina, Paradkar Vikram, Mallubhotla Hanuman, Renukuntla Santosh, Patel Dharmeshkumar, Manoharan Senthilkumar, Panchakshari Mallikarjuna, Kyasani Mahesh, Sengupta Nupur, Martin Laura B, Rossi Omar, Rondini Simona, Giannelli Carlo, Micoli Francesca
Аннотация
INTRODUCTION: Salmonella enterica serovars Typhi and Paratyphi A cause millions of cases and thousands of deaths annually, predominantly affecting children in South and Southeast Asia. Following the licensure and World Health Organization (WHO) prequalification of a typhoid conjugate vaccine (TCV), efforts have focused on developing a bivalent vaccine incorporating an S. Paratyphi A glycoconjugate component to increase vaccine coverage and protection against enteric fever.
METHODS: To create the bivalent vaccine, the S. Paratyphi A serovar-specific O-antigen (O:2) was conjugated to the CRM197 carrier protein using different chemistries. 1-Cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) chemistry was selected based on its simplicity in manufacturing, stability data, and immunogenicity observed in preclinical studies. The final bivalent formulation combined Vi-CRM197 (TCV) for S. Typhi and O:2-CRM197 for S. Paratyphi A. Immunogenicity was evaluated in animal models.
RESULTS: The newly developed bivalent vaccine was stable over time, when stored at 2-8 °C. A slight increase of free O:2 was detected, but remained below 15% after 1 year of storage. In preclinical models, the bivalent formulation elicited strong immune responses against both antigens, higher than the corresponding unconjugated polysaccharides. These results have guided the selection of the formulations to be tested in clinical studies.
CONCLUSIONS: This vaccine has the potential to broaden protection against enteric fever, particularly in high-incidence regions. Further clinical trials are ongoing to confirm efficacy and safety in humans.
METHODS: To create the bivalent vaccine, the S. Paratyphi A serovar-specific O-antigen (O:2) was conjugated to the CRM197 carrier protein using different chemistries. 1-Cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) chemistry was selected based on its simplicity in manufacturing, stability data, and immunogenicity observed in preclinical studies. The final bivalent formulation combined Vi-CRM197 (TCV) for S. Typhi and O:2-CRM197 for S. Paratyphi A. Immunogenicity was evaluated in animal models.
RESULTS: The newly developed bivalent vaccine was stable over time, when stored at 2-8 °C. A slight increase of free O:2 was detected, but remained below 15% after 1 year of storage. In preclinical models, the bivalent formulation elicited strong immune responses against both antigens, higher than the corresponding unconjugated polysaccharides. These results have guided the selection of the formulations to be tested in clinical studies.
CONCLUSIONS: This vaccine has the potential to broaden protection against enteric fever, particularly in high-incidence regions. Further clinical trials are ongoing to confirm efficacy and safety in humans.