Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates
Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates
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DOI：
10.1371/journal.ppat.1000225
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发表时间：
2008-11-01
期刊：
影响因子：
6.7
通讯作者：
Jahrling, Peter B.
中科院分区：
文献类型：
--
作者：
Geisbert, Thomas W.;Daddario-DiCaprio, Kathleen M.;Jahrling, Peter B.
埃博拉病毒（EBOV）是一种重要的人类病原体，作为一种新出现/重新出现的病毒和潜在的生物武器，引起了公共卫生问题。在过去十年中，在开发可以保护非人灵长类动物免受EBOV感染的候选预防性疫苗方面取得了实质性进展。在这些前景中，基于重组水泡性口炎病毒（VSV）的疫苗特别稳健，因为它在作为暴露后治疗给药时也可以提供保护。关于表达EBOV糖蛋白的有复制能力的VSV载体，已经提出的一个问题是这些载体如何被具有改变的或受损的免疫系统的个体（例如感染HIV的患者）耐受。这一点尤其重要，因为迄今为止所有埃博拉病毒疫情都发生在人口中艾滋病毒发病率高的中部和西部非洲地区。为了解决这一问题，我们评估了表达扎伊尔埃博拉病毒糖蛋白（VSV Delta G/ZEBOVGP）的重组VSV载体在感染猴-人免疫缺陷病毒（SHIV）的6只恒河猴中的安全性。所有6只动物均未显示与VSV Delta G/ZEBOVGP疫苗相关的疾病证据，表明该疫苗在免疫功能低下的人群中可能是安全的。虽然该研究的一个目标是评估候选疫苗平台的安全性，但也有兴趣确定改变的免疫状态是否会影响疫苗效力。该疫苗保护了6只SHIV感染的猕猴中的4只在ZEBOV攻击后免于死亡。对所有动物中的CD 4 + T细胞的评估显示，死于致死性ZEBOV攻击的动物具有最低的CD 4+计数，表明CD 4 + T细胞可能在介导针对ZEBOV的保护中起作用。
Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSV Delta G/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSV Delta G/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV.