Signal Transduction and Targeted Therapy (Apr 2022)

Broadly neutralizing antibodies against Omicron-included SARS-CoV-2 variants induced by vaccination

  • Xiangyang Chi,
  • Yingying Guo,
  • Guanying Zhang,
  • Hancong Sun,
  • Jun Zhang,
  • Min Li,
  • Zhengshan Chen,
  • Jin Han,
  • Yuanyuan Zhang,
  • Xinghai Zhang,
  • Pengfei Fan,
  • Zhe Zhang,
  • Busen Wang,
  • Xiaodong Zai,
  • Xuelian Han,
  • Meng Hao,
  • Ting Fang,
  • Jinghan Xu,
  • Shipo Wu,
  • Yi Chen,
  • Yingying Fang,
  • Yunzhu Dong,
  • Bingjie Sun,
  • Jinlong Zhang,
  • Jianmin Li,
  • Guangyu Zhao,
  • Changming Yu,
  • Qiang Zhou,
  • Wei Chen

DOI
https://doi.org/10.1038/s41392-022-00987-z
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 11

Abstract

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Abstract The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time. A monoclonal antibody (mAb), named ZWD12, exhibited potent and broad neutralization against SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa, Delta, and Omicron by blocking the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) and provided complete protection in the challenged prophylactic and therapeutic K18-hACE2 transgenic mouse model. We defined the ZWD12 epitope by determining its structure in complex with the spike (S) protein via cryo-electron microscopy. This study affords the potential to develop broadly therapeutic mAb drugs and suggests that the RBD epitope bound by ZWD12 is a rational target for the design of a broad spectrum of vaccines.