Journal of Vaccine Research 2024, Vol.14, No.4, 170-182 http://medscipublisher.com/index.php/jvr 174 provide balanced protection against all serotypes to prevent severe outcomes such as dengue hemorrhagic fever and dengue shock syndrome, which can result from sequential infections by different serotypes. Studies have shown that vaccines like Dengvaxia (CYD-TDV) demonstrate variable efficacy across the serotypes, with higher efficacy against DENV-3 and DENV-4 and lower efficacy against DENV-1 and DENV-2 (Villar et al., 2015). Similarly, TAK-003, another leading vaccine candidate, has shown robust efficacy against DENV-2 but somewhat lower efficacy against DENV-3 and DENV-4, although the vaccine's overall protection remains strong. This serotype-specific variation in efficacy is a critical consideration for vaccine deployment, particularly in regions where certain serotypes predominate. A vaccine that does not provide adequate protection against all serotypes may lead to a false sense of security, potentially increasing the risk of severe disease in partially protected populations (Hadinegoro et al., 2015). Therefore, ongoing research and vaccine trials continue to focus on achieving more balanced efficacy across all four serotypes. 4.2 Clinical trial outcomes The clinical trial outcomes of dengue vaccines have been pivotal in understanding their efficacy and guiding their use in public health programs. Dengvaxia, the first dengue vaccine to be licensed, was evaluated in several large-scale phase III trials involving over 30 000 participants across Latin America and Asia. These trials demonstrated an overall efficacy of around 60.8% against symptomatic dengue, with notable variation depending on the serotype and age group of the recipients (Villar et al., 2015). However, the vaccine's efficacy was significantly higher in individuals who had prior dengue exposure, raising concerns about its use in seronegative individuals, particularly young children. TAK-003, another prominent candidate, has shown promising results in phase III trials, with an overall efficacy of approximately 80.9% against symptomatic dengue and over 90% efficacy against severe disease requiring hospitalization (Biswal et al., 2019). The vaccine demonstrated consistent protection across both seropositive and seronegative populations, indicating its potential for broader use without the same level of risk identified with Dengvaxia. The ongoing follow-up from these trials continues to provide valuable data on the long-term efficacy and safety of TAK-003. Another candidate, TV003/TV005, has shown robust efficacy in early trials (Figure 2) (Rivera et al., 2022), with high seroconversion rates across all four serotypes following a single dose (Flacco et al., 2024). This vaccine, developed by the National Institute of Allergy and Infectious Diseases (NIAID), is currently undergoing phase III trials, and early results suggest it could offer significant protection with fewer doses than other vaccines (Prompetchara et al., 2020). 4.3 Impact of pre-existing immunity Pre-existing immunity plays a crucial role in the efficacy and safety of dengue vaccines. Individuals who have had prior exposure to one or more dengue virus serotypes generally exhibit stronger immune responses to vaccination and are less likely to experience severe disease upon subsequent infection. This phenomenon was notably observed in the clinical trials of Dengvaxia, where the vaccine's efficacy was significantly higher in seropositive individuals compared to those who were seronegative at the time of vaccination (Hadinegoro et al., 2015). However, in seronegative individuals, particularly young children, Dengvaxia has been associated with an increased risk of severe dengue following vaccination, leading to higher hospitalization rates in this group during post-licensure monitoring. This has raised significant concerns and led to recommendations that Dengvaxia be used only in individuals with confirmed prior dengue infection. In contrast, TAK-003 has shown efficacy in both seropositive and seronegative populations, though the efficacy is generally higher in those with prior immunity. This suggests that while pre-existing immunity enhances vaccine efficacy, TAK-003 may offer safer and more effective protection for all individuals, regardless of their prior exposure status.
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