Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death^1,2,3,4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters^5,6,7 and nonhuman primates^8,9,10 have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates^11,12,13. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.

人类的 2019 冠状病毒病 (COVID-19) 通常是一种临床上较轻的疾病，但有些人会出现严重肺炎、呼吸衰竭和死亡^1,2,3,4 。对仓鼠^5、6、7和非人灵长类动物^8、9、10严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染的研究普遍报告轻度临床疾病，而临床前 SARS-CoV-2 疫苗研究已证明减少非人类灵长类动物上呼吸道和下呼吸道中的病毒复制^11,12,13 。在这里，我们发现仓鼠高剂量鼻内 SARS-CoV-2 感染会导致严重的临床疾病，包括组织中病毒的高水平复制、广泛的肺炎、体重减轻和部分动物的死亡。使用表达稳定的 SARS-CoV-2 刺突蛋白的腺病毒血清型 26 载体疫苗进行单次免疫可引发结合和中和抗体反应，并防止 SARS-CoV-2 引起的体重减轻、肺炎和死亡。这些数据证明疫苗可以预防 SARS-CoV-2 临床疾病。该模型应该对 SARS-CoV-2 疫苗、治疗方法和发病机制的临床前研究有用。