Abstract
Dengue disease is a significant global health issue with nearly 400 million infections per year. Therefore, it is vital to developed a universal dengue vaccine. However, developing such a vaccine faces major challenges including risk of ADE, lack of predictive animal models, and insufficient immunological correlates of protection. First licensed dengue vaccine Dengvaxia showed increased risk of severe dengue likely due to ADE from imbalanced immunity against the four dengue serotypes. This review summarizes current dengue vaccine candidates like Dengvaxia, TAK-003, and TV003/TV005. It highlights the mechanisms and implications of ADE in vaccine-induced immune responses. Potential innovative solutions are discussed including focusing on highly neutralizing epitopes like envelope domain III and leveraging new vaccine platforms such as virus-like particles and mRNA vaccines. These approaches may improve the quality of neutralizing antibodies over cross-reactive enhancement-prone responses. However, definitive immunological correlates for protection remain unknown. Continued research is urgently needed to enable universal dengue vaccine that provides long-lasting immunity against all serotypes without risk of ADE.
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