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A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice.

Authors :
Martinez DR
Schäfer A
Gobeil S
Li D
De la Cruz G
Parks R
Lu X
Barr M
Stalls V
Janowska K
Beaudoin E
Manne K
Mansouri K
Edwards RJ
Cronin K
Yount B
Anasti K
Montgomery SA
Tang J
Golding H
Shen S
Zhou T
Kwong PD
Graham BS
Mascola JR
Montefiori DC
Alam SM
Sempowski G
Sempowski GD
Khurana S
Wiehe K
Saunders KO
Acharya P
Haynes BF
Baric RS
Source :
Science translational medicine [Sci Transl Med] 2022 Jan 26; Vol. 14 (629), pp. eabj7125. Date of Electronic Publication: 2022 Jan 26.
Publication Year :
2022

Abstract

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.

Details

Language :
English
ISSN :
1946-6242
Volume :
14
Issue :
629
Database :
MEDLINE
Journal :
Science translational medicine
Publication Type :
Academic Journal
Accession number :
34726473
Full Text :
https://doi.org/10.1126/scitranslmed.abj7125