Decoding maternal immunity and fetal vulnerability in TBEV vaccination and flavivirus infection

Flaviviruses such as Zika virus (ZIKV), dengue virus (DENV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) cause millions of infections each year and represent a growing global health threat. Climate change, human migration, and vector expansion are driving their spread into new regions, increasing the likelihood of sequential infections and cross-immunity. While congenital ZIKV infection has revealed the devastating impact of flaviviruses during pregnancy, the risks posed by other members, including TBEV, remain largely unexplored. This is of particular concern since TBEV is endemic across large parts of Europe and Asia, where vaccination is commonly recommended, raising important questions about how vaccine-induced immunity may influence responses to subsequent flavivirus infections. The FLAVIPREG project will specifically address these questions in the context of pregnancy, a unique immunological state where maternal tolerance must coexist with antiviral defense. It will investigate how prior TBEV infection or vaccination shapes maternal-fetal susceptibility to heterologous flavivirus infections, with a focus on immune mechanisms, placental transmission, and neurodevelopmental outcomes. Combining advanced mouse pregnancy models, immunoprofiling, single-cell transcriptomics, and high-resolution imaging, the project brings together complementary expertise in maternal-fetal immunology (Singapore) and arbovirology (Czech Republic). Outcomes will provide mechanistic insight into flavivirus pathogenesis during pregnancy and inform vaccination strategies to better protect maternal and neonatal health.