Associated organisationsHarvard University · University of Birmingham · University of LiverpoolEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£1.7M
PeriodMar 2023 — Feb 2026
In plain English
AI plain-English summary
A child in sub-Saharan Africa dies from invasive non-typhoidal *Salmonella* (iNTS) disease every few minutes, yet no vaccine exists. Current vaccine design relies on targeting known bacterial components, but iNTS has no such obvious target. This project abandons that approach. Instead, it will use a technique called Systems Serology to analyse thousands of immune system features in blood samples from African children who are naturally resistant to iNTS and those who are not. By comparing the full antibody profiles of both groups, the researchers aim to let the children’s own immune systems reveal exactly which immune responses provide protection. If successful, this will identify the first robust “correlates of protection” for iNTS—the specific immune signatures a vaccine must elicit. This would immediately guide the refinement of existing experimental iNTS vaccines and accelerate their clinical testing. In the longer term, the same unbiased approach could be applied to other complex bacterial diseases where conventional vaccine design has stalled, providing a template for rational vaccine development that is driven by human immunity rather than pathogen biology.
View original technical description
Most vaccines against bacterial pathogens target toxins or capsules. When not available, less targeted strategies are employed, using live-attenuated vaccines or killed organisms where the necessity to mechanistic understanding is not essential. Historically, such approaches have been extremely beneficial, but looking forward, are likely to provide diminishing returns. A new approach is required, one that is independent of pre-conceptions about the vaccine, but rather approaches vaccine generation by understanding how host and pathogen factors combine to protect. Systems Serology offers a route to identify key mechanistic immunological correlates of protection against diverse diseases by exploiting novel OMIC-technologies. This study will uniquely apply unbiased interdigitated “Systems” level analyses of humoral immune responses to iNTS to comprehensively profile patterns of protective immunity using well-characterised cohorts of susceptible and non-susceptible children, accessed from across Africa. This will guide next generation rational vaccine design, effectively allowing the immune system, rather than the pathogen, to inform the development of effective interventions. These studies will enable the discovery of robust and relevant Correlates of Protection, impacting the translation of early-phase programs of existing first-generation vaccines in the near-term and longer term provide a template for use against other complex diseases accelerating future vaccine implementation.
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