The THAIBRA Alliance: Harnessing prospective studies to delineate the interplay of immunity and pathogen genetics in Zika and dengue

The factors that drove Zika to cause an explosive pandemic in the Americas, yet generate endemic, often silent transmission in Asia remain unknown. We have a unique opportunity to delineate these factors with community cohorts in Brazil and Thailand, which are situated in high DENV transmission settings, but experienced distinctly different Zika burdens and trajectories. We have developed novel assays to interrogate flavivirus antibody and cell-mediated immunity and pioneered methods to reconstruct infection histories from longitudinal data. We will use these approaches to prospectively determine how the flavivirus immune landscape contributes to Zika and dengue risk. Parallel analyses of a cohort of Brazilian mothers and infants will identify the features of the landscape which influence risk heterogeneity for congenital Zika syndrome (CZS). We will augment these studies with robust genomic surveillance to delineate the interplay between population immunity and the transmission potential for ZIKV. If successful, the proposed studies will directly inform medical countermeasures, provide a generalisable approach to identifying regions of ZIKV circulation and susceptibility to future CZS outbreaks, and prioritise sites for intervention trials. This proposal builds on long-standing partnerships with communities and Ministries of Health, ensuring that the evidence generated will be translated to policy and action.