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The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2.

Hualong XiongHui SunSiling WangLunzhi YuanLiqin LiuYuhe ZhuJinlei ZhangYang HuangRuoyao QiYao JiangJian MaMing ZhouYue MaRao FuSiping YanMingxi YueYangtao WuMin WeiYizhen WangTingting LiYingbin WangZizheng ZhengHai YuTong ChengShaowei LiQuan YuanJun ZhangYi GuanQingbing ZhengTianying ZhangNing-Shao Xia
Published in: Proceedings of the National Academy of Sciences of the United States of America (2022)
Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.
Keyphrases
  • sars cov
  • respiratory syndrome coronavirus
  • high resolution
  • gene expression
  • risk assessment
  • mass spectrometry
  • climate change
  • combination therapy