期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 14, 期 629, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.abj7125
关键词
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资金
- Burroughs Wellcome Fund Postdoctoral Enrichment Program Award
- Hanna H. Gray Fellowship from the Howard Hughes Medical Institute
- NIH National Institute of Allergy and Infectious Diseases (NIAID) [T32 AI007151]
- NIAID [F32 AI152296]
- Chan Zuckerberg Initiative
- North Carolina Policy Collaboratory at the University of North Carolina at Chapel Hill
- North Carolina Coronavirus Relief Fund
- NIAID, NIH, U.S. Department of Health and Human Services award [AI157155, U54 CA260543, AI149644, AI145687, AI158571]
- NIH [HHSN272201700036I]
- Intramural Research Program of the Vaccine Research Center, NIAID, NIH
- State of North Carolina
- federal CARES Act
- NIH
- NIAID
- DAIDS [AI142596]
- NCI Cancer Center Core Support Grant [5P30CA016086-41]
- NIH/NIAD [UC6AI058607]
- DOD/DARPA [HR0011-17-2-0069]
- North Carolina Policy Collaboratory at the University of North Carolina at Chapel Hill and Duke University
Severe acute respiratory syndrome coronaviruses (SARS-CoVs), including SARS-CoV-2 variants, can cause deadly infections. A human antibody called DH1047 has been shown to neutralize SARS-CoV and various coronaviruses, and protect against SARS-CoV-2 B.1.351 infection in mice. The study suggests that DH1047 could be a broadly protective antibody and a potential target for a universal sarbecovirus vaccine.
Severe acute respiratory syndrome coronaviruses 1 (SARS-CoV) and 2 (SARS-CoV-2), including SARS-CoV-2 variants of concern, can cause deadly infections. The mortality associated with sarbecovirus infection underscores the importance of developing broadly effective countermeasures against them, which could be key in the prevention and mitigation of current and future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV; bat coronaviruses WIV-1 and RsSHC014; and SARS-CoV-2 variants D614G, B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, B.1.617.1, and B.1.617.2 by a receptor binding domain (RBD)-specific human antibody, DH1047. Prophylactic and therapeutic treatment with DH1047 was protective against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B.1.351 infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among sarbecoviruses. Thus, DH1047 is a broadly protective antibody that can prevent infection and mitigate outbreaks caused by SARS-related strains and SARS-CoV-2 variants. Our results also suggest that the conserved RBD epitope bound by DH1047 is a rational target for a universal sarbecovirus vaccine.
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