Human Infection Studies (360G-Wellcome-216302_Z_19_Z)

Bacillary diarrhoea, including dysentery, due to Shigella causes a high burden of disease in low-and-middle income countries (LMICs), where 70% of all cases occur in children under 5 years. Children in this age group form the target population for disease prevention through vaccination. However, there are no licensed Shigella vaccines in routine use with several candidates still in various stages of clinical development. Shigella human infection studies (HISs) have played a key role in the vaccine development pathway to assess vaccine efficacy, and are established in high income countries (HICs). Adults in LMIC settings are often highly exposed to Shigella with evidence of immunological responses and clinical immunity. HIS in endemic settings provide a unique opportunity to interrogate host immunity and thus inform vaccine development. Furthermore, protective efficacy may vary by population, and efficacy data from HISs in LMIC settings will complement those from HICs in informing clinical development pathways. We will establish a Shigella infection model in an adult endemic population to: (a) demonstrate feasibility and interrogate clinical protection associated in the context of pre-existing immunity; (b) assess vaccine efficacy and candidate selection for advancement; and (c) explore the ethical and social implications of conducting these studies.