Preclinical evaluation of multivalent vaccine combinations againstandinfections.

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, the World Health Organization has included this pathogen among those for which the development of new interventions is a global health priority. No vaccines againstare licensed yet, but several candidates based on the O-antigen portion of lipopolysaccharides are in clinical development, and combining avaccine 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-basedvaccine co-formulated with a bivalentglycoconjugate vaccine targetingTyphi andParatyphi 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 thatGMMA can serve as a carrier for theParatyphi A O-antigen, enabling a formulation with fewer distinct components. The resulting vaccine candidate, combiningandantigens, 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.