Department of Molecular and Comparative Pathobiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
ILAR J. 2021 Dec 31;62(1-2):17-34. doi: 10.1093/ilar/ilab010.
Developing strong animal models is essential for furthering our understanding of how the immune system functions in response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The alarming speed at which SARS-CoV-2 has spread, and the high mortality rate of severe Coronavirus Disease 2019 (COVID-19), has required both basic science and clinical research to move at an unprecedented pace. Models previously developed to study the immune response against SARS-CoV have been rapidly deployed to now study SARS-CoV-2. To date, both small and large animal models are remarkably consistent when infected with SARS-CoV-2; however, certain models have proven more useful when answering specific immunological questions than others. Small animal models, such as Syrian hamsters, ferrets, and mice carrying the hACE2 transgene, appear to reliably recapitulate the initial cytokine surge seen in COVID-19 as well as show significant innate and adaptive cell infiltration in to the lung early in infection. Additionally, these models develop strong antibody responses to the virus, are protected from reinfection, and genetically modified versions exist that can be used to ask specific immunological questions. Large animal models such as rhesus and cynomologus macaques and African green monkeys are critical to understanding how the immune system responds to SARS-CoV-2 infection because they are considered to be the most similar to humans. These models are considered the gold standard for assessing vaccine efficacy and protection, and recapitulate the initial cytokine surge, immune cell infiltration into the lung, certain aspects of thrombosis, and the antibody and T-cell response to the virus. In this review, we discuss both small and large animal model studies previously used in SARS-CoV-2 research that may be useful in elucidating the immunological contributions to hallmark syndromes observed with COVID-19.
开发强大的动物模型对于深入了解免疫系统如何对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染作出反应至关重要。SARS-CoV-2 的传播速度惊人，严重的 2019 年冠状病毒病（COVID-19）的死亡率很高，这使得基础科学和临床研究都必须以前所未有的速度推进。以前用于研究针对 SARS-CoV 的免疫反应的模型已被迅速部署用于研究 SARS-CoV-2。迄今为止，感染 SARS-CoV-2 的小型和大型动物模型都非常一致；然而，某些模型在回答特定免疫学问题时比其他模型更有用。小型动物模型，如叙利亚仓鼠、雪貂和携带 hACE2 转基因的小鼠，似乎可靠地再现了 COVID-19 中最初的细胞因子激增，并在感染早期显示出明显的固有和适应性细胞浸润到肺部。此外，这些模型对病毒产生强烈的抗体反应，免受再感染，并且存在基因修饰版本，可以用于提出特定的免疫学问题。恒河猴、食蟹猴和绿猴等大型动物模型对于理解免疫系统如何对 SARS-CoV-2 感染作出反应至关重要，因为它们被认为与人类最相似。这些模型被认为是评估疫苗效力和保护作用的金标准，并且可以再现最初的细胞因子激增、免疫细胞浸润到肺部、血栓形成的某些方面以及对病毒的抗体和 T 细胞反应。在这篇综述中，我们讨论了以前在 SARS-CoV-2 研究中使用的小型和大型动物模型研究，这些研究可能有助于阐明 COVID-19 中观察到的标志性综合征的免疫学贡献。
