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.IMPORTANCE 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.

中文翻译：

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一种二价球形病毒样颗粒疫苗可增强猕猴对病原性埃博拉病毒的免疫反应广度。

2013-2016年在西非爆发的埃博拉疫情促使人们加快了开发针对这些高毒力病毒的疫苗的工作。一种基于活的重组水疱性口炎病毒的疫苗已在疫情中部署，并且似乎非常有效。单独或与多价修饰牛痘安卡拉（MVA）埃博拉疫苗联合使用的基于复制缺陷型腺病毒载体的疫苗也似乎很有希望，并且正在临床评估中。但是，当前基于活载体的方法预防多种埃博拉病原体的能力尚未建立，引起持久应答可能需要额外的加强疫苗接种。在这里，我们报告了二价的发展，球形埃博拉病毒样颗粒（VLP）疫苗，融合了扎伊尔埃博拉病毒（EBOV）和苏丹埃博拉病毒（SUDV）的糖蛋白（GPs），旨在将免疫范围扩展到EBOV以外。用二价埃博拉病毒VLP免疫兔所产生的抗体可中和埃博拉病毒的所有四种病原体，并引发针对EBOV和SUDV的抗体依赖性细胞介导的细胞毒性（ADCC）反应。用二价VLP接种猕猴可产生强烈的体液免疫反应，包括高滴度的结合以及中和抗体和ADCC反应。VLP疫苗接种导致埃博拉GP特异性CD4和CD8 T细胞反应的频率显着增加。这些结果表明，新型的二价埃博拉VLP疫苗引起了针对病原性埃博拉病毒的强烈体液和细胞免疫反应，并支持对该方法的进一步评估，认为这可能是埃博拉疫苗开发工作的潜在补充。 。尽管已经开发出几种领先的候选埃博拉疫苗，并在临床测试中取得了进展，但可能还需要其他候选疫苗来提供针对不同埃博拉病毒种类的保护并延长保护的持久性。此处展示的一种新方法是在球形核上表达两种遗传上不同的糖蛋白，从而产生可以扩大针对已知病原性埃博拉病毒的免疫反应的疫苗。