Journal of Vaccine Research 2024, Vol.14, No.4, 170-182 http://medscipublisher.com/index.php/jvr 173 Figure 1 LIve attenuated dengue vaccine constructs (Adopted from Thomas, 2023) Image caption: DENV genome components of Sanofi, Takeda, and NIH/Bhutantan/MSD dengue vaccine candidates with the location of known attenutating mutations (Adopted from Thomas, 2023) Another promising candidate is TV003/TV005, developed by the National Institute of Allergy and Infectious Diseases (NIAID). This vaccine is a live-attenuated, tetravalent vaccine that has shown strong immunogenicity and safety profiles in early-phase trials (Walsh et al., 2024). Currently, TV003/TV005 is undergoing phase III trials in several dengue-endemic regions, and early results indicate robust efficacy across all four serotypes with a single dose (Prompetchara et al., 2020). 3.3 Comparison of vaccine platforms The development of dengue vaccines has employed various platforms, each with its own advantages and challenges. The most established platform is live-attenuated vaccines, such as Dengvaxia, TAK-003, and TV003/TV005. These vaccines are designed to elicit a strong and broad immune response by using weakened forms of the virus that mimic natural infection without causing disease. The primary advantage of live-attenuated vaccines is their ability to induce long-lasting immunity with typically fewer doses. However, they pose risks, particularly in seronegative individuals, where there is a potential for enhanced disease if the vaccine does not provide complete protection (Wichmann et al., 2017). In contrast, inactivated vaccines, which use killed virus particles, are generally safer for immunocompromised individuals and seronegative populations since they cannot cause disease. However, inactivated vaccines often require multiple doses and adjuvants to elicit a sufficient immune response. While no inactivated dengue vaccine has reached late-stage clinical trials, this platform remains a potential area for future development. Subunit vaccines, which use specific proteins from the virus rather than the whole virus, offer another approach. These vaccines tend to be very safe and stable, but they often require adjuvants to boost the immune response and may not always induce immunity as robust as live-attenuated vaccines. While subunit vaccines for dengue are still in early stages of development, they represent a promising avenue, especially for populations where live-attenuated vaccines may pose a risk (Guy et al., 2018). While live-attenuated vaccines currently lead the field in dengue vaccine development due to their strong immunogenicity and potential for long-lasting protection, inactivated and subunit vaccines offer safer alternatives that may be more suitable for certain populations (Lin et al., 2021). The ongoing development and trials of these vaccines will be crucial in determining the best strategies for preventing dengue across diverse global populations. 4 Efficacy of Dengue Vaccines 4.1 Efficacy across different serotypes The efficacy of dengue vaccines varies significantly across the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, and DENV-4), posing a unique challenge in vaccine development. An effective dengue vaccine must
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