The Invasive Non-typhoidal Salmonella Vaccine Landscape: Innovations and Challenges Ahead

After years of limited progress, the invasive non-typhoidal Salmonella (iNTS) vaccine pipeline is starting to advance, with a growing number of candidates entering early clinical development.

At Shift Health, our latest review in Vaccine highlights a growing and increasingly diverse pipeline, driven by multiple vaccine approaches. These include:

• Glycoconjugate vaccines: Build on proven technology by linking bacterial polysaccharides to carrier proteins to strengthen and prolong immune responses.
• GMMA (Generalized Modules for Membrane Antigens): Use small particles derived from bacterial membranes to present antigens in a way that closely mimics natural infection, helping the immune system recognize and respond effectively.
• MAPS (Multiple Antigen Presenting System): Combine multiple bacterial components into a single structure in a modular fashion, designed to stimulate a broader and more balanced immune response.

These innovations are particularly important given the significant and growing burden of disease. iNTS remains a leading cause of community-acquired bloodstream infections in sub-Saharan Africa, with case fatality rates as high as 22–47%, and a growing contribution from antimicrobial-resistant strains. Despite this burden, no licensed vaccines currently exist, and the path to licensure remains largely undefined.

From scientific progress to translational readiness

Our review further highlights that while innovation in the pipeline is encouraging, several barriers still need to be addressed to enable successful development, licensure, and uptake:

• Limited epidemiological data to fully characterize disease burden and strain distribution
• No established correlates of protection to guide and accelerate clinical development
• Evolving and uncertain regulatory pathways for vaccines primarily intended for LMIC use
• Limited clinical evidence in key high-risk populations, including young children and people living with HIV

In this context, progress will depend not only on advancing individual candidates, but also on strengthening the broader enabling environment through investment in data generation, clinical infrastructure, and regulatory alignment.

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