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

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Martinez, David R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Schäfer, Alexandra
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Gobeil, Sophie
    • Other Affiliation: Duke University School of Medicine
  • Li, Dapeng
    • Other Affiliation: Duke University School of Medicine
  • De la Cruz, Gabriela
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Parks, Robert
    • Other Affiliation: Duke University School of Medicine
  • Lu, Xiaozhi
    • Other Affiliation: Duke University School of Medicine
  • Barr, Maggie
    • Other Affiliation: Duke University School of Medicine
  • Stalls, Victoria
    • Other Affiliation: Duke University School of Medicine
  • Janowska, Katarzyna
    • Other Affiliation: Duke University School of Medicine
  • Beaudoin, Esther
    • Other Affiliation: Duke University School of Medicine
  • Manne, Kartik
    • Other Affiliation: Duke University School of Medicine
  • Mansouri, Katayoun
    • Other Affiliation: Duke University School of Medicine
  • Edwards, Robert J.
    • Other Affiliation: Duke University School of Medicine
  • Cronin, Kenneth
    • Other Affiliation: Duke University School of Medicine
  • Yount, Boyd
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Anasti, Kara
    • Other Affiliation: Duke University School of Medicine
  • Montgomery, Stephanie A.
    • Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine
  • Tang, Juanjie
    • Other Affiliation: FDA
  • Golding, Hana
    • Other Affiliation: FDA
  • Shen, Shaunna
    • Other Affiliation: Duke University School of Medicine
  • Zhou, Tongqing
    • Other Affiliation: NIH
  • Kwong, Peter D.
    • Other Affiliation: NIH
  • Graham, Barney S.
    • Other Affiliation: NIH
  • Mascola, John R.
    • Other Affiliation: NIH
  • Montefiori, David. C.
    • Other Affiliation: Duke University School of Medicine
  • Alam, S. Munir
    • Other Affiliation: Duke University School of Medicine
  • Sempowski, Gregory D.
    • Other Affiliation: Duke University School of Medicine
  • Khurana, Surender
    • Other Affiliation: FDA
  • Wiehe, Kevin
    • Other Affiliation: Duke University School of Medicine
  • Saunders, Kevin O.
    • Other Affiliation: Duke University School of Medicine
  • Acharya, Priyamvada
    • Other Affiliation: Duke University School of Medicine
  • Haynes, Barton F.
    • Other Affiliation: Duke University School of Medicine
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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, 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
Date of publication
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Science Translational Medicine
Page start
  • eabj7125
Language
  • English

Relations

Parents:

This work has no parents.

In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details scitranslmed.abj7125.pdf 2021-12-01 Public Download