Protection Against Invasive NTS Disease (PAINTS) - correlates of protection towards vaccine licensure

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