A Controlled Human Infection Model of Dengue

This study aims to conduct a safe human infection challenge using an attenuated serotype DEN3 dengue virus in adult volunteers. The clinical, viral and immune response characteristics of the model will be analysed to understand the pathophysiology of dengue fever. This data will be used to inform future studies, including a planned follow up study (DEN-CHIM-02) which will investigate the efficacy of an investigational dengue vaccine at protecting against DEN3 infection. Study conditions that result in a safe, reproducible infection in ≥80% of research participants (attack rate) with the DEN3 challenge agent have been identified during studies conducted by our collaborators in the US. This includes the inoculum dose, safety monitoring, and necessary participant pre-screening to exclude prior Orthoflavivrus infection or vaccinations. Study objectives are to: 1. Establish in seronegative volunteers in Singapore a safe DENV controlled human infection (CHI) model, with an infection rate of ≥80%, suitable for future studies of interventions. 2. Characterise the clinical, haematological and virological response following controlled inoculation of the attenuated DEN3 challenge agent. 3. Conduct deep immunophenotyping to understand the cellular, humoral and innate immune response to dengue infection. 4. Explore the longitudinal immune response in the 3 years after challenge, including following subsequent dengue vaccination.