The COVID-19 pandemic highlighted the clear risk that zoonotic viruses pose to global health and economies. The scientific community responded by developing several efficacious vaccines which were expedited by the global need for vaccines. The emergence of SARS-CoV-2 breakthrough infections highlights the need for additional vaccine modalities to provide stronger, long-lived protective immunity. Here we report the design and preclinical testing of small extracellular vesicles (sEVs) as a multi-subunit vaccine. Cell lines were engineered to produce sEVs containing either the SARS-CoV-2 Spike receptor-binding domain, or an antigenic region from SARS-CoV-2 Nucleocapsid, or both in combination, and we tested their ability to evoke immune responses in vitro and in vivo. B cells incubated with bioengineered sEVs were potent activators of antigen-specific T cell clones. Mice immunised with sEVs containing both sRBD and Nucleocapsid antigens generated sRBD-specific IgGs, nucleocapsid-specific IgGs, which neutralised SARS-CoV-2 infection. sEV-based vaccines allow multiple antigens to be delivered simultaneously resulting in potent, broad immunity, and provide a quick, cheap, and reliable method to test vaccine candidates.

中文翻译：

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生物工程小细胞外囊泡可传递多个 SARS-CoV-2 抗原片段并驱动广泛的免疫反应

COVID-19 大流行凸显了人畜共患病毒对全球健康和经济构成的明显风险。由于全球对疫苗的需求，科学界加快了开发几种有效疫苗的步伐。 SARS-CoV-2 突破性感染的出现凸显了对其他疫苗方式的需求，以提供更强、持久的保护性免疫力。在这里，我们报告了小细胞外囊泡（sEV）作为多亚单位疫苗的设计和临床前测试。细胞系经过工程改造，产生含有 SARS-CoV-2 Spike 受体结合域或 SARS-CoV-2 核衣壳抗原区或两者组合的 sEV，我们测试了它们在体外和体外激发免疫反应的能力。体内。与生物工程 sEV 一起孵育的 B 细胞是抗原特异性 T 细胞克隆的有效激活剂。用含有 sRBD 和核衣壳抗原的 sEV 免疫的小鼠会产生 sRBD 特异性 IgG，即核衣壳特异性 IgG，从而中和 SARS-CoV-2 感染。基于 sEV 的疫苗可以同时递送多种抗原，从而产生有效、广泛的免疫力，并提供一种快速、廉价且可靠的方法来测试候选疫苗。