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- Title
Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses.
- Authors
Li, Mingxi; Ren, Yifei; Aw, Zhen Qin; Chen, Bo; Yang, Ziqing; Lei, Yuqing; Cheng, Lin; Liang, Qingtai; Hong, Junxian; Yang, Yiling; Chen, Jing; Wong, Yi Hao; Wei, Jing; Shan, Sisi; Zhang, Senyan; Ge, Jiwan; Wang, Ruoke; Dong, Jay Zengjun; Chen, Yuxing; Shi, Xuanling
- Abstract
As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines. The authors identify nanobodies from immunized alpaca with broadly neutralizing activity against SARS-CoV-1, SARS-CoV-2 variants, and major sarbecoviruses. One representative nanobody binds to a highly conserved epitope on RBD and protects K18-hACE2 mice from Omicron and Delta infection.
- Subjects
SARS-CoV-2 Omicron variant; SARS-CoV-2; SARS virus; MONOCLONAL antibodies; VACCINE development; ANGIOTENSIN converting enzyme
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-35642-2