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双价、球形病毒样颗粒疫苗增强恒河猴对致病性埃博拉病毒免疫反应的广度。

A Bivalent, Spherical Virus-Like Particle Vaccine Enhances Breadth of Immune Responses against Pathogenic Ebola Viruses in Rhesus Macaques.

机构信息

Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

出版信息

J Virol. 2020 Apr 16;94(9). doi: 10.1128/JVI.01884-19.


DOI:10.1128/JVI.01884-19
PMID:32075939
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7163155/
Abstract

The 2013-2016 Ebola outbreak in West Africa led to accelerated efforts to develop vaccines against these highly virulent viruses. A live, recombinant vesicular stomatitis virus-based vaccine has been deployed in outbreak settings and appears highly effective. Vaccines based on replication-deficient adenovirus vectors either alone or in combination with a multivalent modified vaccinia Ankara (MVA) Ebola vaccine also appear promising and are progressing in clinical evaluation. However, the ability of current live vector-based approaches to protect against multiple pathogenic species of Ebola is not yet established, and eliciting durable responses may require additional booster vaccinations. Here, we report the development of a bivalent, spherical Ebola virus-like particle (VLP) vaccine that incorporates glycoproteins (GPs) from Zaire Ebola virus (EBOV) and Sudan Ebola virus (SUDV) and is designed to extend the breadth of immunity beyond EBOV. Immunization of rabbits with bivalent Ebola VLPs produced antibodies that neutralized all four pathogenic species of Ebola viruses and elicited antibody-dependent cell-mediated cytotoxicity (ADCC) responses against EBOV and SUDV. Vaccination of rhesus macaques with bivalent VLPs generated strong humoral immune responses, including high titers of binding, as well as neutralizing antibodies and ADCC responses. VLP vaccination led to a significant increase in the frequency of Ebola GP-specific CD4 and CD8 T cell responses. These results demonstrate that a novel bivalent Ebola VLP vaccine elicits strong humoral and cellular immune responses against pathogenic Ebola viruses and support further evaluation of this approach as a potential addition to Ebola vaccine development efforts. Ebola outbreaks result in significant morbidity and mortality in affected countries. Although several leading candidate Ebola vaccines have been developed and advanced in clinical testing, additional vaccine candidates may be needed to provide protection against different Ebola species and to extend the durability of protection. A novel approach demonstrated here is to express two genetically diverse glycoproteins on a spherical core, generating a vaccine that can broaden immune responses against known pathogenic Ebola viruses. This approach provides a new method to broaden and potentially extend protective immune responses against Ebola viruses.

摘要

2013-2016 年西非的埃博拉疫情促使人们加速研发针对这些高致病性病毒的疫苗。一种基于活重组水疱性口炎病毒的疫苗已在疫情环境中部署,并显示出高度有效性。基于复制缺陷型腺病毒载体的疫苗,无论是单独使用还是与多价改良痘苗安卡拉(MVA)埃博拉疫苗联合使用,也显示出很有前景,并正在临床评估中进展。然而,目前基于活载体的方法预防多种致病性埃博拉病毒的能力尚未确定,并且可能需要额外的加强免疫来产生持久的反应。在这里,我们报告了一种二价球形埃博拉病毒样颗粒(VLP)疫苗的开发,该疫苗包含来自扎伊尔埃博拉病毒(EBOV)和苏丹埃博拉病毒(SUDV)的糖蛋白(GP),旨在扩大免疫范围超越 EBOV。用二价埃博拉 VLP 免疫兔子产生了中和所有四种致病性埃博拉病毒的抗体,并引发了针对 EBOV 和 SUDV 的抗体依赖性细胞介导的细胞毒性(ADCC)反应。用二价 VLPs 对恒河猴进行疫苗接种产生了强烈的体液免疫反应,包括高滴度的结合抗体以及中和抗体和 ADCC 反应。VLP 疫苗接种导致埃博拉 GP 特异性 CD4 和 CD8 T 细胞反应的频率显著增加。这些结果表明,一种新型的二价埃博拉 VLP 疫苗可针对致病性埃博拉病毒引发强烈的体液和细胞免疫反应,并支持进一步评估这种方法作为埃博拉疫苗开发工作的潜在补充。埃博拉疫情在受影响国家造成了重大的发病率和死亡率。尽管已经开发出几种领先的候选埃博拉疫苗并在临床测试中得到了推进,但可能需要额外的疫苗候选物来提供针对不同埃博拉物种的保护,并延长保护的持久性。这里展示的一种新方法是在球形核心上表达两种遗传上不同的糖蛋白,从而产生一种可以扩大针对已知致病性埃博拉病毒的免疫反应的疫苗。这种方法为扩大和潜在延长针对埃博拉病毒的保护性免疫反应提供了一种新方法。

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本文引用的文献

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