Journal of Vaccine Research 2024, Vol.14, No.4, 170-182 http://medscipublisher.com/index.php/jvr 178 deployment with population-specific epidemiological data to optimize outcomes and minimize risks (Guy et al., 2018). As TAK-003 moves closer to licensure, its implementation in different regions will provide further case studies that could guide future vaccination efforts. The experiences of these early adopter countries will be crucial in refining deployment strategies, particularly in balancing broad coverage with safety and efficacy considerations. 7 Future Directions in Dengue Vaccine Development 7.1 Next-Generation vaccines The future of dengue vaccine development is poised to build on the lessons learned from first-generation vaccines like Dengvaxia and TAK-003. Next-generation vaccines aim to provide broader, safer, and more effective protection against all four dengue virus serotypes, addressing the limitations of existing options. Several emerging vaccine candidates are currently in various stages of development, utilizing innovative platforms that may offer significant advantages over current vaccines. One promising approach involves the development of mRNA vaccines, which have gained global attention following their success in the COVID-19 pandemic. mRNA vaccines are advantageous due to their ability to be rapidly developed and produced at scale, as well as their potential to induce strong and targeted immune responses. Although still in early stages, mRNA-based dengue vaccines could offer more precise immunogenicity and reduce the risks associated with live-attenuated vaccines, particularly in seronegative populations (Prompetchara et al., 2020). Another innovative approach is the development of subunit vaccines, which use specific proteins from the dengue virus to stimulate an immune response without the risks associated with live viruses. These vaccines could potentially offer a safer alternative for populations at higher risk of severe dengue, such as children and immunocompromised individuals. Subunit vaccines are also easier to store and transport, which could improve their deployment in resource-limited settings (Guy et al., 2018). Additionally, there is growing interest in developing vaccines that offer cross-protection against other flaviviruses, such as Zika, which is closely related to dengue. These polyvalent vaccines could be particularly beneficial in regions where multiple flaviviruses co-circulate, reducing the overall burden of these diseases (Wichmann et al., 2017). 7.2 Addressing current limitations Overcoming the limitations of current dengue vaccines is essential for improving their effectiveness and safety, particularly in diverse global populations. One of the most critical challenges is enhancing the efficacy of vaccines in seronegative individuals, who have been shown to be at greater risk of severe dengue following vaccination with Dengvaxia. Future vaccine development strategies are focusing on improving the immune response in these individuals without increasing the risk of antibody-dependent enhancement (ADE). One strategy is to refine the antigenic components of the vaccine to ensure a more balanced immune response across all four serotypes. This could involve the use of new adjuvants that enhance the immune response or the development of vaccine constructs that elicit stronger and more consistent T-cell responses, which are crucial for long-term protection. Another approach is the development of vaccines that require fewer doses to achieve full protection, as this could improve adherence and coverage rates. Single-dose or two-dose regimens are being explored to make vaccination programs more feasible in resource-limited settings, where access to healthcare can be intermittent. Finally, addressing the challenge of ADE through more precise targeting of the immune response remains a top priority. This includes the potential development of vaccines that can be personalized based on an individual's serostatus or immune history, which could help mitigate the risks of severe outcomes following vaccination (Guy et al., 2018).
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