Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Adv Virus Res. 2014;88:315-72. doi: 10.1016/B978-0-12-800098-4.00007-6.
Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The expanding of the habitat of DENV-transmitting mosquitoes has resulted in dramatic increases in the number of cases over the past 50 years, and recent outbreaks have occurred in the United States. Developing a dengue vaccine is a global health priority. DENV vaccine development is challenging due to the existence of four serotypes of the virus (DENV1-4), which a vaccine must protect against. Additionally, the adaptive immune response to DENV may be both protective and pathogenic upon subsequent infection, and the precise features of protective versus pathogenic immune responses to DENV are unknown, complicating vaccine development. Numerous vaccine candidates, including live attenuated, inactivated, recombinant subunit, DNA, and viral vectored vaccines, are in various stages of clinical development, from preclinical to phase 3. This review will discuss the adaptive immune response to DENV, dengue vaccine challenges, animal models used to test dengue vaccine candidates, and historical and current dengue vaccine approaches.
登革病毒（DENV）是热带和亚热带地区发病率和死亡率的重要原因，每年导致数亿感染。感染范围从无症状到自限性发热疾病登革热（DF），到危及生命的登革出血热/登革休克综合征（DHF/DSS）。传播登革病毒的蚊子栖息地的扩大导致过去 50 年来病例数的急剧增加，最近在美国也发生了爆发。开发登革热疫苗是全球卫生的重点。由于病毒存在四种血清型（DENV1-4），疫苗必须针对这四种血清型进行保护，因此登革热疫苗的开发具有挑战性。此外，针对 DENV 的适应性免疫反应在随后的感染中可能既具有保护作用也具有致病性，而针对 DENV 的保护性和致病性免疫反应的具体特征尚不清楚，这使得疫苗的开发变得复杂。包括减毒活疫苗、灭活疫苗、重组亚单位疫苗、DNA 疫苗和病毒载体疫苗在内的多种疫苗候选物处于不同的临床开发阶段，从临床前到 3 期。本文将讨论针对 DENV 的适应性免疫反应、登革热疫苗的挑战、用于测试登革热疫苗候选物的动物模型以及历史和当前的登革热疫苗方法。
