La Jolla Institute for Allergy & Immunology, La Jolla, California, United States of America.
PLoS Pathog. 2013 Oct;9(10):e1003723. doi: 10.1371/journal.ppat.1003723. Epub 2013 Oct 31.
With 2.5 billion people at risk, dengue is a major emerging disease threat and an escalating public health problem worldwide. Dengue virus causes disease ranging from a self-limiting febrile illness (dengue fever) to the potentially fatal dengue hemorrhagic fever/dengue shock syndrome. Severe dengue disease is associated with sub-protective levels of antibody, which exacerbate disease upon re-infection. A dengue vaccine should generate protective immunity without increasing severity of disease. To date, the determinants of vaccine-mediated protection against dengue remain unclear, and additional correlates of protection are urgently needed. Here, mice were immunized with viral replicon particles expressing the dengue envelope protein ectodomain to assess the relative contribution of humoral versus cellular immunity to protection. Vaccination with viral replicon particles provided robust protection against dengue challenge. Vaccine-induced humoral responses had the potential to either protect from or exacerbate dengue disease upon challenge, whereas cellular immune responses were beneficial. This study explores the immunological basis of protection induced by a dengue vaccine and suggests that a safe and efficient vaccine against dengue should trigger both arms of the immune system.
受 25 亿人面临的风险，登革热是一个主要的新兴疾病威胁，也是全球范围内日益严重的公共卫生问题。登革热病毒可引起从自限性发热疾病（登革热）到潜在致命的登革出血热/登革休克综合征等多种疾病。严重登革热疾病与抗体的亚保护水平有关，这会在再次感染时加重疾病。登革热疫苗应产生保护性免疫而不增加疾病的严重程度。迄今为止，针对登革热的疫苗介导保护的决定因素仍不清楚，迫切需要其他保护相关因素。在这里，用表达登革热包膜蛋白外域的病毒复制子颗粒对小鼠进行免疫，以评估体液免疫和细胞免疫对保护的相对贡献。用病毒复制子颗粒进行疫苗接种可提供针对登革热挑战的强大保护。疫苗诱导的体液免疫反应在受到挑战时有可能预防或加重登革热疾病，而细胞免疫反应则有益。本研究探讨了登革热疫苗诱导的保护的免疫学基础，并表明针对登革热的安全有效的疫苗应触发免疫系统的两个分支。
