CBR Division, Defence Science and Technology Laboratory (Dstl), Salisbury SP4 0JQ, UK.
United Kingdom Health and Security Agency, Salisbury SP4 0JG, UK.
Viruses. 2022 Jul 21;14(7):1580. doi: 10.3390/v14071580.
There is an enduring requirement to develop animal models of COVID-19 to assess the efficacy of vaccines and therapeutics that can be used to treat the disease in humans. In this study, six marmosets were exposed to a small particle aerosol (1-3 µm) of SARS-CoV-2 VIC01 that delivered the virus directly to the lower respiratory tract. Following the challenge, marmosets did not develop clinical signs, although a disruption to the normal diurnal temperature rhythm was observed in three out of six animals. Early weight loss and changes to respiratory pattern and activity were also observed, yet there was limited evidence of viral replication or lung pathology associated with infection. There was a robust innate immunological response to infection, which included an early increase in circulating neutrophils and monocytes and a reduction in the proportion of circulating T-cells. Expression of the ACE2 receptor in respiratory tissues was almost absent, but there was ubiquitous expression of TMPRSS2. The results of this study indicate that exposure of marmosets to high concentrations of aerosolised SARS-CoV-2 did not result in the development of clear, reproducible signs of COVID-19.
需要开发 COVID-19 的动物模型,以评估可用于治疗人类疾病的疫苗和疗法的疗效。在这项研究中,六只狨猴暴露于可直接将病毒输送到下呼吸道的 SARS-CoV-2 VIC01 小颗粒气溶胶(1-3 µm)中。在挑战之后,狨猴没有出现临床症状,但在六只动物中有三只出现了正常昼夜体温节律的中断。还观察到早期体重减轻以及呼吸模式和活动的变化,但与感染相关的病毒复制或肺部病理学证据有限。感染引起了强烈的先天免疫反应,包括循环中性粒细胞和单核细胞的早期增加以及循环 T 细胞比例的减少。呼吸道组织中 ACE2 受体的表达几乎不存在,但 TMPRSS2 表达普遍存在。这项研究的结果表明,狨猴暴露于高浓度的气溶胶 SARS-CoV-2 不会导致明确、可重复的 COVID-19 症状的发生。