From promise to pitfalls: immunological lessons from dengue vaccines and their implications

Dengue continues to pose a significant global health threat. However, the development of a safe and effective tetravalent vaccine is impeded by complex serotype-specific and cross-reactive immune responses. This review assesses licensed and advanced dengue vaccines, emphasizing serostatus-dependent safety, serotype imbalance, and the durability of protection. It also critically evaluates immunological correlates of protection and addresses remaining obstacles, such as vector-mediated immune modulation and orthoflavivirus cross-reactivity, to guide future dengue vaccine strategies.