期刊
SCIENCE IMMUNOLOGY
卷 7, 期 76, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.abp9962
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资金
- Howard Hughes Medical Institute
- NIH [HHSN272201600013C, U19AI171413, UL1TR001439]
- Sealy AMP
- Smith Foundation
- Kleberg Foundation
- John S. Dunn Foundation
- Amon G. Carter Foundation
- Gilson Longenbaugh Foundation
- Summerfield Robert Foundation
- CPRIT training grant [RP210041]
The study utilized LIBRA-seq technology to identify an antibody, SW186, that exhibits broad neutralizing activity against various SARS-CoV-2 variants. The cryo-EM structure analysis revealed that SW186 targets a conserved epitope on the receptor binding domain of the viral spike protein. In mouse models, administration of SW186 significantly reduced viral loads in the lungs.
The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as the Omicron variants that are highly transmissible and immune evasive, underscores the need to develop therapeutic antibodies with broad neutralizing activities. Here, we used the LIBRA- seq technology, which identified SARS- CoV-2- specific B cells via DNA barcoding and subsequently single-cell sequenced BCRs, to identify an antibody, SW186, which could neutralize major SARS-CoV-2 variants of concern, including Beta, Delta, and Omicron, as well as SARS-CoV-1. The cryo-EM structure of SW186 bound to the receptor binding domain (RBD) of the viral spike protein showed that SW186 interacted with an epitope of the RBD that is not at the interface of its binding to the ACE2 receptor but is highly conserved among SARS coronaviruses. This epitope encompasses a glycosylation site (N343) of the viral spike protein. Administration of SW186 in mice after they were infected with SARS-CoV-2 Alpha, Beta, or Delta variants reduced the viral loads in the lung. These results demonstrated that SW186 neutralizes diverse SARS coronaviruses by binding to a conserved RBD epitope, which could serve as a target for further antibody development.
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