Updates on Dengue Vaccines; Current Status, Challenges and Future Perspectives

Dengue is a significant public health challenge worldwide. Vector management has become the prime intervention in dengue control. Although various attempts have been made to make a dengue vaccine during the last 3-4 decades, it has become challenging. This review explored the history of dengue vaccine development and its present status and prospects. A literature review from 2010- 2022 covering vaccine development approaches was considered in this study. Significant advancements in vaccine development are evident, with several candidates advancing through clinical trials. The live-attenuated CYD-TDV (Dengvaxia) vaccine by Sanofi Pasteur, the first dengue vaccine approved, has shown variable efficacy and raised safety concerns, especially in dengue-naïve populations. The TAK-003 (Intertypic chimera-DENVax) (Qdenga®) has been approved by the European Medicines Agency (EMA) for use in individuals aged four years and older, based on national guidelines. The TV003/TV005 developed by the National Institutes of Health is currently in Phase III trials. These vaccines aim to address the challenges of antibody-dependent enhancement (ADE) and provide broad, serotypespecific immunity. The live-attenuated vaccines have shown potential, but they face issues like genetic instability and adverse reactions. Non-replicating platforms, such as DNA and subunit vaccines, offer safer alternatives but may need adjuvants to enhance immunogenicity. The review highlights the necessity for ongoing research and innovation to create vaccines that induce strong, protective immune responses without ADE. Despite the approval of Dengvaxia, its limited efficacy in some populations underscores the need for next-generation vaccines that offer comprehensive protection across various demographics.