National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes (NHRI), Miaoli, Taiwan.
Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan.
JCI Insight. 2022 Apr 22;7(8):e157597. doi: 10.1172/jci.insight.157597.
Most therapeutic mAbs target the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. Unfortunately, the RBD is a hot spot for mutations in SARS-CoV-2 variants, which will lead to loss of the neutralizing function of current therapeutic mAbs. Universal mAbs for different variants are necessary. We identified mAbs that recognized the S2 region of the spike protein, which is identical in different variants. The mAbs could neutralize SARS-CoV-2 infection and protect animals from SARS-CoV-2 challenge. After cloning the variable region of the light chain and heavy chain, the variable region sequences were humanized to select a high-affinity humanized mAb, hMab5.17. hMab5.17 protected animals from SARS-CoV-2 challenge and neutralized SARS-CoV-2 variant infection. We further identified the linear epitope of the mAb, which is not mutated in any variant of concern. These data suggest that a mAb recognizing the S2 region of the spike protein will be a potential universal therapeutic mAb for COVID-19.
大多数治疗性单克隆抗体针对 SARS-CoV-2 刺突蛋白的受体结合域（RBD）。不幸的是，RBD 是 SARS-CoV-2 变体中突变的热点，这将导致当前治疗性单克隆抗体失去中和功能。需要针对不同变体的通用单克隆抗体。我们鉴定了识别刺突蛋白 S2 区域的单克隆抗体，该区域在不同变体中是相同的。这些单克隆抗体可以中和 SARS-CoV-2 感染并保护动物免受 SARS-CoV-2 挑战。在克隆轻链和重链的可变区后，对可变区序列进行人源化以选择高亲和力的人源化单克隆抗体 hMab5.17。hMab5.17 可保护动物免受 SARS-CoV-2 挑战，并中和 SARS-CoV-2 变体感染。我们进一步鉴定了该单克隆抗体的线性表位，该表位在任何关注变体中均未发生突变。这些数据表明，识别刺突蛋白 S2 区域的单克隆抗体将成为 COVID-19 的一种有潜力的通用治疗性单克隆抗体。
