A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice
Year: 2021
Type: article
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
DOI: 10.17615/s4n5-5505
Authors: Barr, Maggie, Acharya, Priyamvada, Stalls, Victoria, Saunders, Kevin O., Yount, Boyd, Tang, Juanjie, Sempowski, Gregory D., Kwong, Peter D., Parks, Robert, Mascola, John R., Mansouri, Katayoun, Montgomery, Stephanie A., Edwards, Robert J., Zhou, Tongqing, Schäfer, Alexandra, Graham, Barney S., De la Cruz, Gabriela, Manne, Kartik, Khurana, Surender, Golding, Hana, Beaudoin, Esther, Janowska, Katarzyna, Montefiori, David. C., Shen, Shaunna, Alam, S. Munir, Gobeil, Sophie, Lu, Xiaozhi, Wiehe, Kevin, Martinez, David R., Li, Dapeng, Haynes, Barton F., Baric, Ralph S., Cronin, Kenneth, Anasti, Kara
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, Vaccine Research Center, National Institutes of Health, Defense Advanced Research Projects Agency, University of North Carolina at Chapel Hill, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Awards: G1249107499, G1741978266, G2099865330, Defining viral and immune mechanisms of Dengue virus serotype 2 immune evasion, G2944681526, G3194372699, G3279675593, North Carolina Seronet Center for Excellence, G4408947578, G5137654827, G5247632879, G542087556, G59380150, Data commons for 'omic, microscopy and analysis core facilities, G63705990, G7759720476, G7790317656, G8267975637, G8312716606, G9000048827, G9000079728, G9000127194, G9000293526, Cancer Center Support Grant
OpenAlex ID: W4287435762