Journal of Vaccine Research 2024, Vol.14, No.4, 170-182 http://medscipublisher.com/index.php/jvr 172 The early efforts in dengue vaccine development, particularly with live-attenuated vaccines, provided critical insights into the complexities of inducing safe and effective immunity against all four dengue serotypes. These lessons continue to inform the development of next-generation vaccines and the strategies for their implementation. 3 Current Leading Dengue Vaccine Candidates 3.1 Overview of available vaccines As of today, Dengvaxia (CYD-TDV), developed by Sanofi Pasteur, remains the most prominent dengue vaccine that has received regulatory approval (Table 1). Dengvaxia is a live-attenuated, tetravalent vaccine that was first licensed in 2015 for use in individuals aged 9-45 years in dengue-endemic areas. This vaccine is based on a chimeric yellow fever virus backbone, incorporating the envelope proteins of all four dengue serotypes to elicit an immune response (Guy et al., 2016). Despite its efficacy in preventing severe dengue and reducing hospitalizations, Dengvaxia has faced significant challenges, particularly due to its variable efficacy across different serotypes and safety concerns in seronegative individuals, especially children (Halstead, 2022). These concerns have led to restricted use, with the World Health Organization (WHO) recommending the vaccine only for individuals who have had a prior dengue infection (Hadinegoro et al., 2015). Table 1 Dengue vaccine candidates in use or in clinical trials (Adopted from Deng et al., 2020) Vaccine Type Name Strategy Clinical Trial Phase Live Attenuated vaccine CYD-TDV Replacing the prM/E gene of the YF17D virus with genes of the DENV1–4 Evaluation after part of the license TV003/TV005 Attenuation by truncating 30 nucleotides in the 3′ UTR of DENV1, DENV3, DENV4, and a chimeric DENV2/DENV4 Phase III DENVax Replacing the coding sequences of DENV2 PDK-53 attenuated vaccine with that of DENV1, DENV3, and DENV4 Phase III Inactivated virus PIV Purified formalin-inactivated virus and adjuvants Phase I Subunit vaccine V180 A recombinant truncated protein containing DEN-80E Phase I DNA vaccine D1ME100 Recombinant plasmid vector encoding prM/E Phase I TVDV Recombinant plasmid vector encoding prM/E proteins of DENV1–4 Phase I Heterologous prime/boost TLAV Prime/PIV boost and reverse order Initial immune-boost strategy Phase I Table caption: CYD-TDV: the live attenuated chimeric yellow fever 17D virus-tetravalent dengue vaccine; DENVax: the live attenuated tetravalent dengue vaccine; PIV: the purified formalin-inactivated virus vaccine; TVDV: the tetravalent DNA vaccine; TLAV: the tetra-live attenuated virus vaccine (Adopted from Deng et al., 2020) 3.2 Leading candidates in late-stage trials Beyond Dengvaxia, several other dengue vaccine candidates are in late-stage clinical trials, offering hope for more effective and safer alternatives (Thomas, 2023). Among these, TAK-003, developed by Takeda Pharmaceuticals, stands out as a leading candidate. TAK-003 is a live-attenuated vaccine based on a DENV-2 backbone and is engineered to express the envelope proteins of the other three serotypes, aiming to provide balanced immunity across all four serotypes (Figure 1). In phase III trials, TAK-003 demonstrated an overall efficacy of approximately 80% against symptomatic dengue and 90% against dengue requiring hospitalization. Importantly, this efficacy was observed across both seropositive and seronegative individuals, suggesting a broader applicability than Dengvaxia (Biswal et al., 2021).
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