AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.
State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Carol Yu Center for Infection, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Clinical Microbiology and Infection Control, the University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, PRC.
Cell Host Microbe. 2021 Apr 14;29(4):551-563.e5. doi: 10.1016/j.chom.2021.02.019. Epub 2021 Feb 25.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a burst in the upper respiratory portal for high transmissibility. To determine human neutralizing antibodies (HuNAbs) for entry protection, we tested three potent HuNAbs (IC range, 0.0007-0.35 μg/mL) against live SARS-CoV-2 infection in the golden Syrian hamster model. These HuNAbs inhibit SARS-CoV-2 infection by competing with human angiotensin converting enzyme-2 for binding to the viral receptor binding domain (RBD). Prophylactic intraperitoneal or intranasal injection of individual HuNAb or DNA vaccination significantly reduces infection in the lungs but not in the nasal turbinates of hamsters intranasally challenged with SARS-CoV-2. Although postchallenge HuNAb therapy suppresses viral loads and lung damage, robust infection is observed in nasal turbinates treated within 1-3 days. Our findings demonstrate that systemic HuNAb suppresses SARS-CoV-2 replication and injury in lungs; however, robust viral infection in nasal turbinate may outcompete the antibody with significant implications to subprotection, reinfection, and vaccine.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）以上呼吸道门户的爆发为特征，具有高度传染性。为了确定针对进入保护的人类中和抗体（HuNAb），我们在金黄地鼠模型中针对活 SARS-CoV-2 感染测试了三种有效的 HuNAb（IC 范围为 0.0007-0.35μg/ml）。这些 HuNAb 通过与人类血管紧张素转换酶 2 竞争结合病毒受体结合域（RBD）来抑制 SARS-CoV-2 感染。针对 SARS-CoV-2 的经腹腔或鼻腔内预防性注射个体 HuNAb 或 DNA 疫苗可显著减少肺部感染，但不能减少鼻腔鼻甲的感染。尽管在感染后给予 HuNAb 治疗可抑制病毒载量和肺损伤，但在 1-3 天内治疗鼻腔鼻甲时仍可观察到强烈的感染。我们的研究结果表明，全身性 HuNAb 可抑制 SARS-CoV-2 在肺部的复制和损伤；然而，鼻腔鼻甲中的强烈病毒感染可能会与抗体竞争，这对亚保护、再感染和疫苗具有重要意义。
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