Sengupta, A. and Bhattacharyya, J. Overcoming Challenges in Dengue Vaccine Development: Advanced Delivery Approaches. Mol Pharm, 2026 Feb 15, PMID: 41693158
This paper addresses the critical global health challenge posed by dengue virus, emphasizing the complexities in developing a safe, effective, and long-lasting vaccine capable of protecting against all four serotypes. Given the limitations of existing vaccines, such as serotype skewing and the risk of antibody-dependent enhancement (ADE), the authors highlight innovative approaches, including advanced delivery systems, rational antigen design, and novel platforms like mRNA and cell-free vaccines, that aim to overcome these hurdles. The review underscores the urgent need for improved vaccination strategies to combat the widespread impact of dengue, especially in resource-limited settings, and advocates for integrating scientific innovation, computational tools, and scalable technologies to facilitate safer, more durable immunity worldwide.
The paper discusses saponins, particularly QS-21, as promising adjuvants for dengue vaccines due to their immunomodulatory properties. QS-21 is known to promote Th1-biased immune responses, which are beneficial for protective immunity against intracellular pathogens like dengue virus. Studies have shown that QS-21 can enhance the breadth and diversity of neutralizing antibodies and synergize with other adjuvants such as synthetic lipid A, forming liposomal formulations that provide prolonged protection in animal models. These formulations not only boost neutralizing antibody levels but also contribute to long-lasting immunity, underscoring QS-21’s potential to improve vaccine efficacy against dengue.
Most promising approaches and the future directions in dengue vaccine development include: Nanoparticle-based delivery systems (including lipid nanoparticles and VLPs); mRNA vaccine platforms; In silico antigen and epitope design; Combination adjuvants (along with saponin-based molecules like QS-21) that activate innate immunity to elicit balanced Th1/Th2 responses and long-lasting immunity.
Link: https://pubmed.ncbi.nlm.nih.gov/41693158/
