Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy.
Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy.
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DOI：
10.1126/science.abc4730
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发表时间：
2020-09-25
期刊：
影响因子：
--
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Gu H;Chen Q;Yang G;He L;Fan H;Deng YQ;Wang Y;Teng Y;Zhao Z;Cui Y;Li Y;Li XF;Li J;Zhang NN;Yang X;Chen S;Guo Y;Zhao G;Wang X;Luo DY;Wang H;Yang X;Li Y;Han G;He Y;Zhou X;Geng S;Sheng X;Jiang S;Sun S;Qin CF;Zhou Y
在开发治疗严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染的医学干预措施所必需的研究工具中，最重要的是研究病毒发病机制的信息丰富的动物模型。Gu等人开发了一种小鼠模型，其中SARS-CoV-2菌株具有感染性，可引起炎症反应和中度肺炎。该病毒株在小鼠中的适应似乎依赖于病毒刺突蛋白的受体结合结构域内的关键氨基酸变化，Asn 501至Tyr（N501 Y）。新的小鼠模型用于研究中和抗体和针对该病毒的候选疫苗。SARS-CoV-2小鼠模型用于研究病毒反应和候选疫苗的开发。2019年冠状病毒病（COVID-19）大流行正在持续，因此开发严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的小动物模型成为优先事项。我们通过在老年BALB/c小鼠的呼吸道中连续传代来适应SARS-CoV-2的临床分离物。在第6代得到的小鼠适应菌株（称为MASCp 6）显示小鼠肺中的感染性增加，并在鼻内接种后导致年轻和老年小鼠的间质性肺炎和炎症反应。深度测序揭示了一组适应性突变，可能与毒力增加有关。特别地，N501 Y突变位于刺突蛋白的受体结合结构域（RBD）。通过使用该模型验证了重组RBD疫苗候选物的保护效力。因此，这种小鼠适应的菌株和相关的挑战模型应该是有价值的评估疫苗和抗病毒药物对SARS-CoV-2。
Among the research tools necessary to develop medical interventions to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, high on the list are informative animal models with which to study viral pathogenesis. Gu et al. developed a mouse model in which a SARS-CoV-2 strain was infectious and could cause an inflammatory response and moderate pneumonia. Adaptation of this viral strain in the mouse appeared to be dependent on a critical amino acid change, Asn501 to Tyr (N501Y), within the receptor-binding domain of the viral spike protein. The new mouse model was used to study neutralizing antibodies and a vaccine candidate against the virus. Science, this issue p. 1603 A SARS-CoV-2 mouse model is used to study viral responses and the development of vaccine candidates. The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.
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作者：
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DOI：
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发表时间：
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发表时间：
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期刊：
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