Serotype-structured force of infection for optimizing dengue vaccine trial design

Dengue fever, transmitted primarily by Aedes aegypti, remains a major global public health threat, causing an estimated 390 million infections annually. Designing efficient dengue vaccine efficacy trials in endemic regions is challenging because transmission intensity varies across space and time, baseline population immunity is heterogeneous, and endpoint accrual depends strongly on the local force of infection (FoI). We developed a simulation framework for trial planning in endemic settings that links FoI to age-specific seroprevalence through a catalytic model and then translates FoI into symptomatic endpoint incidence for randomized controlled trial simulations. Across a range of FoI scenarios representing low-to-high endemic transmission, we evaluated sample size requirements, follow-up duration, and expected power under alternative vaccine efficacy assumptions. In high-transmission settings, the framework indicates that trials enrolling 5,000-10,000 participants per arm can achieve at least 80% power within 12-24 months of follow-up under plausible symptomatic detection assumptions. Sensitivity analyses demonstrate that feasibility thresholds are most sensitive to FoI and the symptomatic fraction, highlighting the importance of site selection and surveillance intensity. Overall, the proposed FoI-based approach provides practical guidance for dengue trial design, including sample size determination, follow-up planning, and the identification of epidemiological conditions under which vaccine evaluation is most efficient in endemic settings.