Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-31259-7
Keywords
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Categories
Funding
- Hong Kong Research Grants Council Collaborative Research Fund [C7156-20G, C1134-20G, C5110-20G]
- Shenzhen Science and Technology Program [JSGG20200225151410198, JCYJ20210324131610027]
- Health@InnoHK, Innovation and Technology Commission
- Government of the Hong Kong Special Administrative Region
- National Program on Key Research Project of China [2020YFC0860600, 2020YFA0707500, 2020YFA0707504]
- Friends of Hope Education Fund in Hong Kong
- Hong Kong Theme-Based Research Scheme [T11-706/18N]
- Wellcome Trust [P86433]
- Health and Medical Research Fund
- Food and Health Bureau
- Government of the Hong Kong Special Administrative Region [COVID1903010-Project 7, COVID190123, 20190572, 19181012]
- Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for Department of Health of the Government of the Hong Kong Special Administrative Region
- Sanming Project of Medicine in Shenzhen, China [SZSM201911014]
- High Level-Hospital Program, Health Commission of Guangdong Province, China
- Major Science and Technology Program of Hainan Province [ZDKJ202003]
- research project of Hainan academician innovation platform [YSPTZX202004]
- Shaw Foundation of Hong Kong
- Richard Yu and Carol Yu, Michael Seak-Kan Tong, May Tam Mak Mei Yin, Lee Wan Keung Charity Foundation Limited
- Providence Foundation Limited
- Hong Kong Sanatorium & Hospital, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited
- Chan Yin Chuen Memorial Charitable Foundation
- Marina Man-Wai Lee
- Hong Kong Hainan Commercial Association South China Microbiology Research Fund
- Jessie & George Ho Charitable Foundation
- Perfect Shape Medical Limited
- Kai Chong Tong
- Tse Kam Ming Laurence
- Foo Oi Foundation Limited
- Betty Hing-Chu Lee
- Ping Cham So
- Lo Ying Shek Chi Wai Foundation
- Lo Kwee Seong Foundation
- Research Grants Council (RGC) of Hong Kong [ECS26101919, GRF16103321, C7009-20GF, C6001-21EF]
- Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) [SMSEGL20SC01-L]
- Guangdong Natural Science Foundation [GDST21SC04]
- Shenzhen Science and Technology Innovation Committee [SZSZSTI2108]
- HKUST start-up and initiation grants
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Here, researchers successfully screened and isolated a broadly neutralizing antibody ZCB11 that can neutralize all variants of concern of SARS-CoV-2, showing particularly potent activity against the Omicron variant. Further studies demonstrated that ZCB11 predominantly interacts with the receptor-binding domain of the Omicron variant, blocking ACE2 binding. Prophylactic or therapeutic administration of ZCB11 protected against lung infection in animal models challenged with the Omicron variant.
The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the efficacy of current vaccines and antibody immunotherapy. Here, we screen 34 BNT162b2-vaccinees and isolate a public broadly neutralizing antibody ZCB11 derived from the IGHV1-58 family. ZCB11 targets viral receptor-binding domain specifically and neutralizes all SARS-CoV-2 variants of concern, especially with great potency against authentic Omicron and Delta variants. Pseudovirus-based mapping of 57 naturally occurred spike mutations or deletions reveals that S371L results in 11-fold neutralization resistance, but it is rescued by compensating mutations in Omicron variants. Cryo-EM analysis demonstrates that ZCB11 heavy chain predominantly interacts with Omicron spike trimer with receptor-binding domain in up conformation blocking ACE2 binding. In addition, prophylactic or therapeutic ZCB11 administration protects lung infection against Omicron viral challenge in golden Syrian hamsters. These results suggest that vaccine-induced ZCB11 is a promising broadly neutralizing antibody for biomedical interventions against pandemic SARS-CoV-2. SARS-CoV-2 variants of concern such as the Omicron variant pose a challenge for vaccination and antibody immunotherapy. Here, Zhou et al. isolate a broadly neutralizing antibody (bNAb), named ZCB11, that protects Golden Syrian hamsters against Omicron. Applying CryoEM the authors show that ZCB11 heavy chain predominantly interacts with RBD in up confirmation, which interferes with ACE2 receptor binding.
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