ShigAfriCoP: Unravelling immune signatures against Shigella to inform multivalent vaccine approaches

Shigella is the most common cause of diarrhoea among children in low-and- middle income countries (LMICs). However, there is no licenced vaccine and no definitive correlate(s) of protection to accelerate vaccine development. Individuals in LMICs are repeatedly exposed and develop immunity. Deliberate infection of adults in human infection studies (HIS) plays a key role in selecting vaccine candidates but has not yet been fully exploited to identify correlates of protection in the context of naturally acquired immunity. We will use existing samples and datasets in four work packages (WPs): WP1) Human infection studies (HIS) in (a) a Kenyan cohort of adults with prior exposure and (b) a vaccine-efficacy HIS study in the USA; WP2) longitudinal cohort of children under 5 years with severe shigellosis from Zambia and Burkina Faso; WP3) age-stratified, cross-sectional community survey samples from individuals in Burkina Faso and Kenya; and WP4) samples from two vaccine trials. This proposal is uniquely placed to identify and validate correlate(s) of protection by bringing together resources from HIS, studies of severe illness and community surveys, and vaccine trials to progress through discovery of correlates (WP1) and validation (WP2) to application for vulnerable populations (WP3) and testing immunity raised by vaccination (WP4).