The ongoing coronavirus disease 2019 (COVID-19) pandemic has spurred rapid development of vaccines as part of the public health response. However, the general strategy used to construct recombinant trimeric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) proteins in mammalian cells is not completely adaptive to molecular farming. Therefore, we generated several constructs of recombinant S proteins for high expression in Nicotiana benthamiana. Intramuscular injection of N. benthamiana-expressed S_ct vaccine (NS_ctVac) into Balb/c mice elicited both humoral and cellular immune responses, and booster doses increased neutralizing antibody titres. In human angiotensin-converting enzyme knock-in mice, two doses of NS_ctVac induced anti-S and neutralizing antibodies, which cross-neutralized Alpha, Beta, Delta and Omicron variants. Survival rates after lethal challenge with SARS-CoV-2 were up to 80%, without significant body weight loss, and viral titres in lung tissue fell rapidly, with no infectious virus detectable at 7-day post-infection. Thus, plant-derived NS_ctVac could be a candidate COVID-19 vaccine.

中文翻译：

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在本塞姆氏烟草中表达的 SARS-CoV-2 刺突三聚体疫苗，辅以明矾，可在小鼠中引发保护性免疫反应


作为公共卫生应对措施的一部分，持续不断的 2019 年冠状病毒病 (COVID-19) 大流行刺激了疫苗的快速开发。然而，在哺乳动物细胞中构建重组三聚体严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 刺突 (S) 蛋白的一般策略并不完全适应分子农业。因此，我们生成了几种重组S蛋白构建体，用于在本塞姆氏烟草中高表达。将本塞姆氏烟草表达的 S _ct疫苗（NS _ct Vac）肌内注射到 Balb/c 小鼠中，引发体液和细胞免疫反应，并且加强剂量增加了中和抗体滴度。在人血管紧张素转换酶敲入小鼠中，两剂 NS _ct Vac 诱导抗 S 抗体和中和抗体，从而交叉中和 Alpha、Beta、Delta 和 Omicron 变体。 SARS-CoV-2致命攻击后的存活率高达80%，体重没有明显下降，肺组织中的病毒滴度迅速下降，感染后7天没有检测到传染性病毒。因此，植物源性 NS _ct Vac 可能是候选的 COVID-19 疫苗。