The invasive non-typhoidal Salmonella vaccine landscape: Innovations and challenges ahead.

Invasive non-typhoidal Salmonella disease represents a major public health challenge, particularly in sub-Saharan Africa, where it is a leading cause of community-acquired bloodstream infections. Despite its significant morbidity and mortality, no licensed vaccines exist. Recognizing this unmet need, multiple global health initiatives and targeted investments have advanced iNTS vaccine development. These efforts have advanced several promising candidates employing diverse platform technologies, including the first iNTS vaccine candidate to enter clinical trials in more than 15 years in 2019. To date, three additional candidates have entered clinical development-two progressing through Phase 2 trials and one currently in a Phase 1/2 study-while many more remain in preclinical development. Several candidates also incorporate antigens targeting Salmonella Typhi or Salmonella Paratyphi A alongside iNTS components to broaden coverage and expand market potential. Despite this progress, scientific, regulatory and commercial challenges persist. In response, global health organizations have intensified efforts to support vaccine development, clarify regulatory pathways and foster engagement with key decision-makers, including through the development of Preferred Product Characteristics and a Full Value of Vaccines Assessment. These coordinated efforts mark a significant step toward enabling and accelerating iNTS vaccine development, ultimately aiming to prevent iNTS disease and its associated health burden.