National Institute For Viral Disease Control and Prevention, Chinese Center For Disease Control and Prevention, Beijing, China.
Special Pathogen Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
Vaccine. 2018 Oct 1;36(41):6053-6060. doi: 10.1016/j.vaccine.2018.09.003. Epub 2018 Sep 6.
Ebola virus (EBOV) disease (EVD) leads to lethal hemorrhagic fever with a case fatality rate as high as 90%, thus posing a serious global public health concern. However, while several vaccines based on the EBOV glycoprotein have been confirmed to be effective in animal experiments, no licensed vaccines or effective treatments have been approved since the first outbreak was reported in 1976. In this study, we prepared the extracellular domain of the EBOV GP protein (designated as N20) by prokaryotic expression and purification via chromatography. Using CTA1-DD (designated as H45) as a mucosal adjuvant, we evaluated the immunogenicity of N20 by intranasal administration and the associated protective efficacy against mouse-adapted EBOV challenge in mice. We found that intranasal vaccination with H45-adjuvanted N20 could stimulate humoral immunity, as supported by GP-specific IgG titers; Th1 cellular immunity, based on IgG subclasses and IFN-γ/IL-4 secreting cells; and mucosal immunity, based on the presence of anti-EBOV IgA in vaginal lavages. We also confirmed that the vaccine could completely protect mice against a lethal mouse-adapted EBOV (MA-EBOV) challenge with few side effects (based on weight loss). In comparison, mice that received N20 or H45 alone succumbed to lethal MA-EBOV challenge. Therefore, mucosal vaccination with H45-adjuvanted N20 represents a potential vaccine candidate for the prevention of EBOV in an effective, safe, and convenient manner.
埃博拉病毒（EBOV）病导致致命性出血热，病死率高达 90%，因此对全球公共卫生构成严重威胁。然而，尽管已有几种基于 EBOV 糖蛋白的疫苗在动物实验中被证实有效，但自 1976 年首次报告暴发以来，尚无获得许可的疫苗或有效治疗方法。在这项研究中，我们通过原核表达和色谱纯化制备了 EBOV GP 蛋白的细胞外结构域（命名为 N20）。使用 CTA1-DD（命名为 H45）作为黏膜佐剂，我们通过鼻腔内给药评估了 N20 的免疫原性及其在小鼠中对适应小鼠的 EBOV 攻击的相关保护效力。我们发现，鼻腔内接种 H45 佐剂的 N20 可以刺激体液免疫，这得到了 GP 特异性 IgG 滴度的支持；Th1 细胞免疫，基于 IgG 亚类和 IFN-γ/IL-4 分泌细胞；以及黏膜免疫，基于阴道冲洗液中存在抗 EBOV IgA。我们还证实，该疫苗可以完全保护小鼠免受致命性适应小鼠的 EBOV（MA-EBOV）攻击，且副作用很少（根据体重减轻情况判断）。相比之下，单独接受 N20 或 H45 的小鼠则死于致命性 MA-EBOV 攻击。因此，用 H45 佐剂的 N20 进行黏膜接种是一种有潜力的疫苗候选物，可有效、安全且方便地预防 EBOV。
