Tan Brandon E K, Tham Seng Kong, Poh Chit Laa
ALPS Global Holding Berhad, The Icon, East Wing Tower Level 18-01 & Level 18-02, No. 1 Jalan 1/68F, Off Jalan Tun Razak, Kuala Lumpur 50400, Malaysia.
Nilai University, No.1, Persiaran Universiti, Putra Nilai, Bandar Baru Nilai, Nilai 71800, Malaysia.
Vaccines (Basel). 2025 May 16;13(5):532. doi: 10.3390/vaccines13050532.
Dengue virus (DENV) threatens public health, especially in regions with tropical and subtropical climates. In 2024, the World Health Organisation reported 3.4 million confirmed dengue cases, with 16,000 severe cases and 3000 dengue-associated fatalities. The first licensed dengue vaccine, CYD-TDV (Dengvaxia,Sanofi-Pasteur, Paris, France), is recommended by the WHO only for individuals aged 9-45 years with a prior history of dengue infection. However, being vaccinated with Dengvaxia increases the risk of developing severe dengue infections in seronegative individuals. Recently, a second licensed dengue vaccine, Qdenga,Takeda, Singen, Germany), was approved and recommended by the WHO to be administered only in highly dengue-endemic countries, as it was not shown to elicit a robust immune response against DENV-3 and DENV-4 serotypes in dengue seronegative individuals. Due to an imbalance in immune response against all four DENV serotypes, there is a higher risk of developing the antibody-dependent enhancement (ADE) effect, which could lead to severe dengue. This review has identified mutations throughout the DENV genome that were demonstrated to attenuate the virulence of DENV in either in vitro or in vivo studies. Several amino acid residues within the DENV prM and E proteins were identified to play important roles in ADE and modifying these ADE-linked residues is important in the rational design of novel live-attenuated dengue vaccine candidates. This review provides current insights to guide the development of a novel live-attenuated tetravalent dengue vaccine candidate that is effective against all DENV serotypes and safe from ADE. The efficacy and safety of the live-attenuated vaccine candidate should be further validated in in vivo studies.
登革病毒（DENV）对公众健康构成威胁，尤其是在热带和亚热带气候地区。2024年，世界卫生组织报告了340万例确诊登革热病例，其中16000例为重症病例，3000例与登革热相关的死亡病例。首个获得许可的登革热疫苗CYD-TDV（Dengvaxia，赛诺菲巴斯德公司，法国巴黎），世界卫生组织仅推荐给有登革热感染史的9至45岁个体。然而，接种Dengvaxia会增加血清阴性个体发生严重登革热感染的风险。最近，第二个获得许可的登革热疫苗Qdenga（武田公司，德国辛根）被世界卫生组织批准并推荐仅在登革热高度流行国家使用，因为在登革热血清阴性个体中，它未显示出对DENV-3和DENV-4血清型产生强大的免疫反应。由于针对所有四种DENV血清型的免疫反应不平衡，发生抗体依赖性增强（ADE）效应的风险更高，这可能导致严重登革热。本综述确定了DENV基因组中的突变，这些突变在体外或体内研究中均被证明可减弱DENV的毒力。已确定DENV prM和E蛋白内的几个氨基酸残基在ADE中起重要作用，修饰这些与ADE相关的残基对于新型减毒活登革热疫苗候选株的合理设计很重要。本综述提供了当前的见解，以指导开发一种新型减毒活四价登革热疫苗候选株，该候选株对所有DENV血清型均有效且无ADE风险。减毒活疫苗候选株的有效性和安全性应在体内研究中进一步验证。
