DEVELOPMENT OF DENGUE VACCINE: FROM MOLECULAR DESIGN AND IMMUNOGENICITY TO EFFECTIVE PROTECTION IN REAL-WORLD SETTINGS BY USING AI-DRIVEN.

Abstract

Dengue continues to pose a significant global public health issue, with four antigenically distinct serotypes of the dengue virus (DENV) leading to considerable morbidity in tropical and subtropical areas. The creation of an effective dengue vaccine has been hindered by factors such as viral genetic diversity, serotype-specific immunity, antibody-dependent enhancement, and inconsistent vaccine efficacy among different populations. This review provides a critical analysis of the progression in dengue vaccine development, covering aspects from rational molecular design and antigen selection to immunogenicity, clinical efficacy, and real-world protection. It evaluates contemporary vaccine platforms, including live-attenuated, recombinant, viral-vector, DNA, mRNA, and virus-like particle technologies, focusing on their ability to elicit balanced and long-lasting humoral and cellular immune responses against all four DENV serotypes. Special emphasis is placed on structural vaccinology, epitope engineering, antigen optimization, and strategies aimed at reducing the risk of antibody-dependent enhancement. The review integrates evidence from preclinical studies and clinical trials with emerging data on real-world effectiveness and safety to evaluate vaccine performance across various epidemiological contexts. Additionally, it underscores the impact of prior dengue exposure, age, serostatus, viral genotype, and transmission intensity on vaccine outcomes. Future advancements that incorporate computational vaccine design, artificial intelligence, systems immunology, and next-generation delivery platforms may facilitate broader, safer, and more enduring protection. Together, these advancements offer a translational framework for expediting the development of next-generation dengue vaccines from molecular innovation to effective population-level disease prevention.