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An Allelotyping PCR for Identifying Salmonella enterica serovars Enteritidis, Hadar, Heidelberg, and Typhimurium
Published on: July 22, 2011
Preclinical evaluation of a bivalent conjugate vaccine against Salmonella Typhi and Paratyphi A
Renzo Alfini1, Roberta Di Benedetto1, Martina Carducci1
1GSK Vaccines Institute for Global Health, Siena, Italy.
Insights
A new bivalent vaccine combining typhoid conjugate vaccine (TCV) and Salmonella Paratyphi A components shows promise for broader enteric fever protection. Preclinical studies demonstrate stability and strong immune responses, guiding human clinical trials.
Area of Science:
- Vaccinology
- Microbiology
- Immunology
Background:
- Salmonella enterica serovars Typhi and Paratyphi A cause significant global enteric fever burden, particularly in South and Southeast Asia.
- Existing typhoid conjugate vaccines (TCV) offer protection against S. Typhi, but coverage against S. Paratyphi A remains limited.
Purpose of the Study:
- To develop and evaluate a novel bivalent vaccine against S. Typhi and S. Paratyphi A.
- To assess the stability and immunogenicity of the bivalent vaccine in preclinical models.
Main Methods:
- Conjugation of S. Paratyphi A O-antigen (O:2) to CRM197 carrier protein using CDAP chemistry.
- Formulation of a bivalent vaccine combining Vi-CRM197 (TCV) and O:2-CRM197.
- Evaluation of vaccine stability at 2-8°C and immunogenicity in animal models.
Main Results:
- The bivalent vaccine demonstrated good stability over one year of storage at 2-8°C.
- Preclinical models showed robust immune responses against both S. Typhi and S. Paratyphi A antigens.
- The bivalent formulation elicited stronger immune responses than unconjugated polysaccharides.
Conclusions:
- The developed bivalent vaccine is stable and immunogenic in preclinical studies.
- This vaccine holds potential for expanded protection against enteric fever in high-incidence regions.
- Clinical trials are underway to confirm human efficacy and safety.
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.
