Department of Molecular and Cellular Sciences, Faculty of Advanced Sciences & Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, 194193311, Iran.
Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
Appl Microbiol Biotechnol. 2018 Apr;102(7):2977-2996. doi: 10.1007/s00253-018-8822-y. Epub 2018 Feb 22.
Dengue viruses are emerging mosquito-borne pathogens belonging to Flaviviridae family which are transmitted to humans via the bites of infected mosquitoes Aedes aegypti and Aedes albopictus. Because of the wide distribution of these mosquito vectors, more than 2.5 billion people are approximately at risk of dengue infection. Dengue viruses cause dengue fever and severe life-threatening illnesses as well as dengue hemorrhagic fever and dengue shock syndrome. All four serotypes of dengue virus can cause dengue diseases, but the manifestations are nearly different depending on type of the virus in consequent infections. Infection by any serotype creates life-long immunity against the corresponding serotype and temporary immunity to the others. This transient immunity declines after a while (6 months to 2 years) and is not protective against other serotypes, even may enhance the severity of a secondary heterotypic infection with a different serotype through a phenomenon known as antibody-depended enhancement (ADE). Although, it can be one of the possible explanations for more severe dengue diseases in individuals infected with a different serotype after primary infection. The envelope protein (E protein) of dengue virus is responsible for a wide range of biological activities, including binding to host cell receptors and fusion to and entry into host cells. The E protein, and especially its domain III (EDIII), stimulates host immunity responses by inducing protective and neutralizing antibodies. Therefore, the dengue E protein is an important antigen for vaccine development and diagnostic purposes. Here, we have provided a comprehensive review of dengue disease, vaccine design challenges, and various approaches in dengue vaccine development with emphasizing on newly developed envelope domain III-based dengue vaccine candidates.
登革热病毒是属于黄病毒科的新兴蚊媒病原体，通过受感染的埃及伊蚊和白纹伊蚊的叮咬传播给人类。由于这些蚊子媒介的广泛分布，超过 25 亿人面临登革热感染的风险。登革热病毒会导致登革热和严重危及生命的疾病，以及登革出血热和登革休克综合征。所有四种登革热病毒血清型都可引起登革热疾病，但由于随后感染的病毒类型不同，其表现几乎不同。任何一种血清型的感染都会对相应的血清型产生终身免疫力，并对其他血清型产生暂时免疫力。这种短暂的免疫力会在一段时间后下降（6 个月至 2 年），并且不能对其他血清型起到保护作用，甚至可能通过一种称为抗体依赖增强作用（ADE）的现象加剧不同血清型的二次异型感染的严重程度。虽然，这可能是初次感染后感染不同血清型的个体中更严重登革热疾病的原因之一。登革热病毒的包膜蛋白（E 蛋白）负责广泛的生物学活性，包括与宿主细胞受体结合以及与宿主细胞融合和进入宿主细胞。E 蛋白，特别是其结构域 III（EDIII），通过诱导保护性和中和抗体来刺激宿主免疫反应。因此，登革热 E 蛋白是疫苗开发和诊断目的的重要抗原。在这里，我们全面回顾了登革热疾病、疫苗设计挑战以及登革热疫苗开发的各种方法，重点介绍了新开发的基于包膜结构域 III 的登革热疫苗候选物。
