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

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.

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