Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge
Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge
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DOI：
10.1016/j.ebiom.2019.09.055
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发表时间：
2019-11-01
期刊：
影响因子：
11.1
通讯作者：
Feldmann, Heinz
中科院分区：
文献类型：
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作者：
Marzi, Andrea;Reynolds, Pierce;Feldmann, Heinz
背景：埃博拉病毒 (EBOV) 变种 Makona 是 2013 年至 2016 年西非疫情的病原体，导致近 30,000 人感染和 11,000 多人死亡。疫情期间，通过人体临床试验，加速了多种实验性疫苗的研发。其中之一，基于水泡性口炎病毒（VSV）的疫苗VSV-EBOV，在几内亚的三期临床试验中显示出良好的疗效，目前用于刚果民主共和国（DRC）东北部正在爆发的埃博拉病毒疫情。该疫苗将 1995 年爆发的 EBOV-Kikwit 糖蛋白表达为免疫原。方法：在这里，我们生成了一种基于 VSV 的疫苗，表达当代 EBOV-Makona 糖蛋白。我们在组织培养中表征了疫苗，并分析了食蟹猴模型中的疫苗功效。随后，我们确定了非人灵长类动物针对致命性 EBOV 攻击的剂量依赖性保护功效。结果：我们观察到，使用 1 x10(7) 至 1 x10(1) 噬菌斑形成单位的 VSV-EBOV 剂量可完全预防疾病。一些接受较低剂量疫苗的受保护动物出现暂时性低水平埃博拉病毒血症。对照动物在攻击后一周内出现典型的埃博拉病毒疾病并达到安乐死标准。这项研究表明，极低剂量的 VSV-EBOV 可以一致地保护猕猴免受致命的 EBOV 攻击。解释：我们的研究提供了缺失的临床前数据，支持在不降低保护功效的情况下减少 VSV-EBOV 疫苗剂量的使用，同时提高疫苗的安全性和可用性——这是公共卫生应对中的两个关键问题。资金来源：美国国立卫生研究院国家过敏和传染病研究所校内研究部。由 Elsevier B.V. 出版
Background: Ebola virus (EBOV), variant Makona, was the causative agent of the 2013-2016 West African epidemic responsible for almost 30,000 human infections and over 11,000 fatalities. During the epidemic, the development of several experimental vaccines was accelerated through human clinical trials. One of them, the vesicular stomatitis virus (VSV)-based vaccine VSV-EBOV, showed promising efficacy in a phase 3 clinical trial in Guinea and is currently used in the ongoing EBOV outbreak in the northeastern part of the Democratic Republic of the Congo (DRC). This vaccine expresses the EBOV-Kikwit glycoprotein from the 1995 outbreak as the immunogen.Methods: Here we generated a VSV-based vaccine expressing the contemporary EBOV-Makona glycoprotein. We characterized the vaccine in tissue culture and analyzed vaccine efficacy in the cynomolgus macaque model. Subsequently, we determined the dose-dependent protective efficacy in nonhuman primates against lethal EBOV challenge.Findings: We observed complete protection from disease with VSV-EBOV doses ranging from 1 x10(7) to 1 x10(1) plaque-forming units. Some protected animals receiving lower vaccine doses developed temporary low-level EBOV viremia. Control animals developed classical EBOV disease and reached euthanasia criteria within a week after challenge. This study demonstrates that very low doses of VSV-EBOV uniformly protect macaques against lethal EBOV challenge. Interpretation: Our study provides missing pre-clinical data supporting the use of reduced VSV-EBOV vaccine doses without decreasing protective efficacy and at the same time increase vaccine safety and availability - two critical concerns in public health response.Funding: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Published by Elsevier B.V.