Establishing Shigella Human Infection Studies in an endemic population in Kenya for evaluating Shigella vaccines

This is a joint application that will leverage expertise spanning regulatory, ethical, clinical, and laboratory to establish Shigella human infection studies (HIS) at two sites in Kenya, Kericho and Kilifi. 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 who 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 have played a key role in the vaccine development pathway to assess vaccine efficacy. Thus, the goal is to successfully establish Shigella HISs in Kenya. This will be achieved by: (a) conducting dose-finding and dose verification Shigella studies that safely and reproducibly induce ≥60% attack rates under the guidance of experienced clinicians and scientists; (b) assessing vaccine efficacy against a Shigella serotype that is impractical in more traditional field efficacy studies; and (c) explore the ethical and social implications of conducting these studies in a LMIC setting. Once established, the model will accelerate Shigella vaccine development by facilitating the early selection of the most promising vaccines for more extensive testing in LMICs.