An ideal protective vaccine against SARS-CoV-2 should not only be effective in preventing disease, but also in preventing virus transmission. It should also be well accepted by the population and have a simple logistic chain. To fulfill these criteria, we developed a thermostable, orally administered vaccine that can induce a robust mucosal neutralizing immune response. We used our platform based on retrovirus-derived enveloped virus-like particles (e-VLPs) harnessed with variable surface proteins (VSPs) from the intestinal parasite Giardia lamblia, affording them resistance to degradation and the triggering of robust mucosal cellular and antibody immune responses after oral administration. We made e-VLPs expressing various forms of the SARS-CoV-2 Spike protein (S), with or without membrane protein (M) expression. We found that prime-boost administration of VSP-decorated e-VLPs expressing a pre-fusion stabilized form of S and M triggers robust mucosal responses against SARS-CoV-2 in mice and hamsters, which translate into complete protection from a viral challenge. Moreover, they dramatically boosted the IgA mucosal response of intramuscularly injected vaccines. We conclude that our thermostable orally administered e-VLP vaccine could be a valuable addition to the current arsenal against SARS-CoV-2, in a stand-alone prime-boost vaccination strategy or as a boost for existing vaccines.

中文翻译：

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一种耐热的口服 SARS-CoV-2 疫苗可诱导粘膜免疫和保护性免疫

针对 SARS-CoV-2 的理想保护性疫苗不仅应能有效预防疾病，还应能预防病毒传播。它也应该被人们很好地接受，并且具有简单的物流链。为了满足这些标准，我们开发了一种耐热的口服疫苗，可以诱导强大的粘膜中和免疫反应。我们使用了基于逆转录病毒衍生的包膜病毒样颗粒 (e-VLP) 的平台，并利用来自肠道寄生虫贾第鞭毛虫的可变表面蛋白 (VSP)，使它们能够抵抗降解并在口服后引发强大的粘膜细胞和抗体免疫反应。我们制作了表达各种形式的 SARS-CoV-2 Spike 蛋白 (S) 的 e-VLP，有或没有膜蛋白 (M) 表达。我们发现，对表达融合前稳定形式的 S 和 M 的 VSP 修饰的 e-VLP 进行启动增强给药，可在小鼠和仓鼠中触发针对 SARS-CoV-2 的强大粘膜反应，这转化为完全保护免受病毒攻击。此外，它们显着增强了肌肉注射疫苗的 IgA 粘膜反应。我们得出的结论是，我们的耐热口服 e-VLP 疫苗可能是对当前针对 SARS-CoV-2 的武器库的宝贵补充，无论是在独立的初始免疫接种策略中，还是作为现有疫苗的增强剂。