Challenge agent strain selection and characterization for a first-in-human Salmonella Typhimurium controlled human infection model
Nontyphoidal Salmonella (NTS) infections cause significant illness worldwide, particularly in sub-Saharan Africa, where invasive NTS (iNTS) disease leads to life-threatening bloodstream infections. Developing vaccines to prevent iNTS is a public health priority, but progress has been slow due to gaps in understanding how these bacteria cause disease and how the immune system responds. Controlled human infection models (CHIMs) can accelerate vaccine development by allowing detailed investigation of infection biology in a controlled setting.  This study describes the selection, production, and detailed characterisation of two Salmonella Typhimurium strains for the first-in-human iNTS CHIM. The strains – one associated with diarrhoeal disease and the other with bloodstream infections – were chosen based on their global relevance and comprehensive prior testing. We confirmed their stability, antibiotic susceptibility, and behaviour in conditions mimicking the human gut. Importantly, we found that sodium bicarbonate, used to neutralise stomach acid before infection, does not alter bacterial virulence.  These findings ensure that the selected strains accurately represent real-world infections while maintaining safety for use in human trials. This CHIM will be a valuable platform for testing new iNTS vaccines and improving our understanding of NTS infections. Overall design: RNA-seq profiling of Salmonella Typhimurium strain 4/74 and D23580 before and after 30 minute bicarbonate treatment.