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

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.

• Authors: David R Martinez, Alexandra Schäfer, Sophie Gobeil, Dapeng Li, Gabriela De la Cruz, Robert Parks, Xiaozhi Lu, Maggie Barr, Victoria Stalls, Katarzyna Janowska, Esther Beaudoin, Kartik Manne, Katayoun Mansouri, Robert J Edwards, Kenneth Cronin, Boyd Yount, Kara Anasti, Stephanie A Montgomery, Juanjie Tang, Hana Golding, Shaunna Shen, Tongqing Zhou, Peter D Kwong, Barney S Graham, John R Mascola, David C Montefiori, S Munir Alam, Gregory Sempowski, Gregory D Sempowski, Surender Khurana, Kevin Wiehe, Kevin O Saunders, Priyamvada Acharya, Barton F Haynes, Ralph S Baric
• Journal: Science translational medicine (Sci Transl Med) Vol. 14 Issue 629 Pg. eabj7125 (Jan 26 2022) ISSN: 1946-6242 [Electronic] United States
• PMID: 34726473 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• DH1047
• Spike Glycoprotein, Coronavirus

Topics

• Animals
• Antibodies, Neutralizing
• Antibodies, Viral
• COVID-19
• Humans
• Mice
• SARS-CoV-2
• Spike Glycoprotein, Coronavirus