As emerging and re-emerging pathogens, filoviruses, especially Ebola virus (EBOV), pose a great threat to public health and require sustained attention and ongoing surveillance. More vaccines and antiviral drugs are imperative to be developed and stockpiled to respond to unpredictable outbreaks. Virus-like vesicles, generated by alphavirus replicons expressing homogeneous or heterogeneous glycoproteins (GPs), have demonstrated the capacity of self-propagation and shown great potential in vaccine development. Here, we describe a novel class of EBOV-like vesicles (eVLVs) incorporating both EBOV GP and VP40. The eVLVs exhibited similar antigenicity as EBOV. In murine models, eVLVs were highly attenuated and elicited robust GP-specific antibodies with neutralizing activities. Importantly, a single dose of eVLVs conferred complete protection in a surrogate EBOV lethal mouse model. Furthermore, our VLVs strategy was also successfully applied to Marburg virus (MARV), the representative member of the genus Marburgvirus. Taken together, our findings indicate the feasibility of an alphavirus-derived VLVs strategy in combating infection of filoviruses represented by EBOV and MARV, which provides further evidence of the potential of this platform for universal live-attenuated vaccine development.

中文翻译：

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以埃博拉病毒糖蛋白为疫苗的自扩增病毒样囊泡的合理设计


作为新出现和重新出现的病原体，丝状病毒，尤其是埃博拉病毒 （EBOV），对公共卫生构成巨大威胁，需要持续关注和持续监测。必须开发和储备更多的疫苗和抗病毒药物，以应对不可预测的疫情。由表达均相或异质性糖蛋白 （GP） 的甲病毒复制子产生的病毒样囊泡已证明具有自我繁殖的能力，并在疫苗开发中显示出巨大潜力。在这里，我们描述了一类新型的 EBOV 样囊泡 （eVLV），同时结合了 EBOV GP 和 VP40。eVLVs 表现出与 EBOV 相似的抗原性。在小鼠模型中，eVLVs 高度减弱并引发具有中和活性的稳健 GP 特异性抗体。重要的是，单剂量的 eVLV 在替代 EBOV 致死小鼠模型中提供完全保护。此外，我们的 VLV 策略也成功地应用于马尔堡病毒 （MARV），马尔堡病毒属的代表成员。综上所述，我们的研究结果表明甲病毒衍生的 VLV 策略在对抗以 EBOV 和 MARV 为代表的丝状病毒感染方面的可行性，这进一步证明了该平台在普遍减毒活疫苗开发方面的潜力。