Volume 7 Issue 5, May 2022:
Article
Broadly neutralizing antibodies against Omicron-included SARS-CoV-2 variants induced by vaccination
Xiangyang Chi,Yingying Guo,Guanying Zhang,Hancong Sun,Jun Zhang
ORCID: orcid.org/0000-0002-9650-112X,Min Li,Zhengshan Chen,Jin Han,Yuanyuan Zhang,Xinghai Zhang,Pengfei Fan,Zhe Zhang,Busen Wang
ORCID: orcid.org/0000-0001-9041-1919,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
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.
