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《Science，9月25日，Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-10-14

  • Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy
    View ORCID ProfileHongjing Gu1,*, View ORCID ProfileQi Chen1,*, View ORCID ProfileGuan Yang2,*, View ORCID ProfileLei He1,*, View ORCID ProfileHang Fan1,*, View ORCID ProfileYong-Qiang Deng1,*, Yanxiao Wang2, Yue...

    Science  25 Sep 2020:
    Vol. 369, Issue 6511, pp. 1603-1607
    DOI: 10.1126/science.abc4730

    Abstract
    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.

  • 原文来源：https://science.sciencemag.org/content/369/6511/1603
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  • 《Science，7月30日，Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-08-18
    • Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy View ORCID ProfileHongjing Gu1,*, View ORCID ProfileQi Chen1,*, View ORCID ProfileGuan Yang2,*, View ORCID ProfileLei He1,*, View ORCID ProfileHang Fan1,*, View ORCID ProfileYong-Qiang Deng1,*, Yanxiao Wang2, Yue Teng1, View ORCID ProfileZhongpeng Zhao1, View ORCID ProfileYujun Cui1, Yuchang Li1, View ORCID ProfileXiao-Feng Li1, View ORCID ProfileJiangfan Li1, View ORCID ProfileNa-Na Zhang1, View ORCID ProfileXiaolan Yang1, Shaolong Chen1, Yan Guo1, View ORCID ProfileGuangyu Zhao1, View ORCID ProfileXiliang Wang1, De-Yan Luo1, Hui Wang1, View ORCID ProfileXiao Yang2, Yan Li3, Gencheng Han3, Yuxian He4, Xiaojun Zhou5, Shusheng Geng6, Xiaoli Sheng6, View ORCID ProfileShibo Jiang7,†,‡, View ORCID ProfileShihui Sun1,†,‡, View ORCID ProfileCheng-Feng Qin1,†,‡, View ORCID ProfileYusen Zhou1,‡,§ See all authors and affiliations Science  30 Jul 2020: eabc4730 DOI: 10.1126/science.abc4730 Abstract The ongoing COVID-19 pandemic has prioritized the development of small animal models for SARS-CoV-2. Herein, 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 (termed MASCp6) showed increased infectivity in mouse lung, and led to interstitial pneumonia and inflammatory responses in both young and aged mice following 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 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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  • 《7月30日_科学家测试SARS-CoV-2在BALB/c小鼠中的适应性以评估疫苗功效》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-08-18
    • 军事医学科学院、北京生命科学研究院、军事认知与脑科学研究所、中国医学科学院北京协和医学院、北京乔恩生物制品有限公司和复旦大学的科研人员在Science期刊上发表题为“Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy”的文章。 开发用于SARS-CoV-2的小动物模型已被列为优先事项。研究人员在老年BALB/c小鼠的呼吸道中通过连续传代筛选出了一株SARS-CoV-2临床分离株。产生的第6代小鼠适应菌株（称为MASCp6）在小鼠肺中表现出增强的感染能力，鼻内接种后，幼龄小鼠和老年小鼠体内产生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性增加有关，特别是N501Y突变位于spike蛋白的受体结合区域（RBD）。该模型验证了重组RBD候选疫苗的保护效果，因此，这种小鼠适应毒株和相关的挑战模型在评估抗SARS-CoV-2的疫苗和抗病毒药物方面具有价值。 原文链接： https://science.sciencemag.org/content/early/2020/07/29/science.abc4730
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