Advancing dengue vaccine development: Challenges, innovations, and the path toward global protection.

Dengue fever remains a significant global health threat, placing nearly half of the world's population at risk. Despite decades of research, developing an effective dengue vaccine continues to face multiple challenges, including antibody-dependent enhancement (ADE), serotype-specific efficacy, and logistical barriers to vaccine delivery. This review provides a comprehensive analysis of the historical and current landscape of dengue vaccine development, focusing on CYD-TDV, TAK-003, and Butantan-DV. It examines their efficacy, safety profiles, and limitations, particularly in achieving balanced quadrivalent protection. Additionally, this review highlights key areas for future research, including the impact of ADE, advancements in vaccine platforms, the need for region-specific vaccine formulations, and the integration of vaccination into broader dengue prevention strategies. Ultimately, sustained investment and global collaboration are crucial for achieving the goal of a dengue-free world.