Associated organisationsImperial College London · National Institute of Biomedical Research · Kamuzu University of Health Sciences · University of Birmingham · University of Liverpool · University of OxfordEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£5.1M
PeriodNov 2024 — Nov 2027
In plain English
AI plain-English summary
A single blood test could determine whether a new vaccine against a deadly bloodstream infection in Africa is working, clearing the way for its approval. Invasive Non-Typhoid Salmonella (iNTS) disease kills thousands of children in sub-Saharan Africa each year. Two vaccines are already in early human trials, but no one knows what level of immune response actually protects against infection. Without that knowledge, regulators cannot approve the vaccines for widespread use. This project will standardise a laboratory test that measures antibodies against the key component of the Salmonella bacterium—the O-antigen. Researchers will analyse blood samples from infected patients, healthy people in high-risk areas, and volunteers in controlled infection studies. They will also examine how these antibodies work alongside other immune defences, such as T-cells and IgA antibodies. If the test is validated, it could serve as a formal “correlate of protection” for vaccine licensure. That would allow phase 3 trials to proceed more quickly and cheaply, and ultimately save lives by enabling rapid deployment of an effective vaccine across Africa. The work also strengthens African research networks capable of running future field trials.
View original technical description
Invasive Non-Typhoid Salmonella (iNTS) disease is a high-burden high-fatality bloodstream infection across Africa, associated with young age and malaria. Two candidate-vaccines (conjugate and membrane-based) against the commonest serovars (Typhimurium and Enteritidis) are in phase 1b/2a clinical development. Lipolysaccharide O-antigen is a central antigen in both. We will standardise a putative Correlate of Protection (CoP) ELISA assay of IgG against candidate-vaccine serotype-specific lipopolysacharide O-antigens (OAg). We will use exposed/immune sera from diverse groups including: infected/re-challenged individuals in a Controlled Human Infection Model (CHIM); acute/convalescent, and asymptomatically-exposed cohorts in two high- incidence African settings; and vaccine clinical trial samples; to characterise anti-OAg IgG responses. Using ex-vivo and in-vivo models we will use sera to describe the relationships of anti-O IgG with anti-OAg IgA/M, functional cellular and humoral protective mechanisms. We will model the relationships of anti-O IgG and their functional co-correlates with iNTS susceptibility and protection at the population level and individual level, to understand the impacts of susceptibilities and force-of-infection on protective threshold, and to understand vaccine impact and durability of protection. These will validate a standardized assay supporting a direct licensure pathway and phase 3 clinical trials, and create mature collaborative African networks with growing CHIM and field trial capacity
Identifying correlates of protection to support vaccine development
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