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Updated: May 9, 2026
A High-throughput Shigella-specific Bactericidal Assay
Published on: February 27, 2019
Preclinical evaluation of multivalent vaccine combinations against Shigella and Salmonella infections
Roberta Di Benedetto1,2, Rebecca Nappini1, Salvatore Gemmellaro1
1GSK Vaccines Institute for Global Health (GVGH), Siena, Italy.
Insights
A new combination vaccine strategy combines Shigella and Salmonella antigens in animal models. This approach shows technical feasibility and potential to reduce disease burden and antimicrobial resistance.
Area of Science:
- Vaccinology
- Microbiology
- Immunology
Background:
- Shigellosis causes severe diarrhea, particularly in young children in low-resource settings.
- Rising antimicrobial resistance in Shigella necessitates new interventions, as prioritized by the WHO.
- No Shigella vaccines are currently licensed, but candidates are in development, with combination strategies recommended.
Purpose of the Study:
- To present a novel combination vaccine strategy for Shigella and Salmonella.
- To assess the technical feasibility of co-formulating Shigella GMMA with Salmonella Typhi and Paratyphi A glycoconjugate vaccines.
- To evaluate the impact on humoral immune responses and explore antigen carrier potential.
Main Methods:
- Development of a tetravalent Shigella GMMA-based vaccine co-formulated with a bivalent Salmonella glycoconjugate vaccine.
- Testing in animal models to assess immunogenicity and technical feasibility.
- Investigating the Shigella GMMA as a carrier for Salmonella Paratyphi A O-antigen.
Main Results:
- Demonstrated technical feasibility of combining six antigens without compromising humoral immune responses.
- Showed that Shigella GMMA can act as a carrier for Salmonella Paratyphi A O-antigen, simplifying formulation.
- The combined vaccine elicited immune responses to all components in animal models.
Conclusions:
- A novel combination vaccine targeting Shigella, Salmonella Typhi, and Salmonella Paratyphi A is technically feasible.
- This strategy has the potential to improve vaccine acceptance, reduce costs, and combat antimicrobial resistance.
- Further development could lead to a valuable tool for reducing the global burden of diarrheal diseases.
Abstract:
Shigellosis is an intestinal infection causing severe and often life-threatening diarrheal disease, with high prevalence in children under five years of age in low- and middle-income countries. Given the rise of antimicrobial resistance to Shigella, the World Health Organization has included this pathogen among those for which the development of new interventions is a global health priority. No vaccines against Shigella are licensed yet, but several candidates based on the O-antigen portion of lipopolysaccharides are in clinical development, and combining a Shigella vaccine with another vaccine has recently been recommended to broaden protection while minimizing the need for additional injections in an already crowded childhood immunization schedule. Here, in animal models, we present a novel combination vaccine strategy: a tetravalent GMMA-based Shigella vaccine co-formulated with a bivalent Salmonella glycoconjugate vaccine targeting S. Typhi and S. Paratyphi A, the causative agents of typhoid and paratyphoid fever. We demonstrate the technical feasibility of combining all six antigens without major impact on the humoral immune response to any component. Moreover, we show that Shigella GMMA can serve as a carrier for the S. Paratyphi A O-antigen, enabling a formulation with fewer distinct components. The resulting vaccine candidate, combining Shigella and Salmonella antigens, has the potential to enhance vaccine acceptance and uptake, facilitate programmatic roll-out, reduce delivery costs, and contribute to reducing disease burden and antimicrobial resistance.
