Preclinical evaluation of multivalent vaccine combinations against Shigella and Salmonella infections

Shigellosis is an intestinal infection causing severe and often life-threatening diarrheal disease, with high prevalence in children under five years of age in lowand 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.