A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice-Reference-Cited by-同舟云学术

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

Published:2022-01-26 Issue:629 Volume:14 Page:
ISSN:1946-6234
Container-title:Science Translational Medicine
language:en
Short-container-title:Sci. Transl. Med.

Author:

Martinez David R.¹^ORCID,Schäfer Alexandra¹^ORCID,Gobeil Sophie²^ORCID,Li Dapeng²,De la Cruz Gabriela³^ORCID,Parks Robert²^ORCID,Lu Xiaozhi²^ORCID,Barr Maggie²,Stalls Victoria²^ORCID,Janowska Katarzyna²,Beaudoin Esther²^ORCID,Manne Kartik²^ORCID,Mansouri Katayoun²,Edwards Robert J.²^ORCID,Cronin Kenneth²^ORCID,Yount Boyd¹,Anasti Kara²^ORCID,Montgomery Stephanie A.⁴^ORCID,Tang Juanjie⁵,Golding Hana⁵,Shen Shaunna⁶^ORCID,Zhou Tongqing⁷^ORCID,Kwong Peter D.⁷^ORCID,Graham Barney S.⁷^ORCID,Mascola John R.⁷^ORCID,Montefiori David C.⁶^ORCID,Alam S. Munir^ORCID,Sempowski Gregory²^ORCID,Sempowski Gregory D.²^ORCID,Khurana Surender⁵^ORCID,Wiehe Kevin²^ORCID,Saunders Kevin O.²⁶^ORCID,Acharya Priyamvada²⁶^ORCID,Haynes Barton F.²^ORCID,Baric Ralph S.¹^ORCID

Affiliation:

1. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

2. Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.

3. Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

4. Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

5. Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, USA.

6. Department of Surgery, Duke University School of Medicine, Durham, NC, USA.

7. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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