The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2

Cathcart A.L., Havenar-Daughton C., Lempp F.A., Ma D., Schmid M.A., Agostini M.L., Guarino B., Di iulio J., Rosen L.E., Tucker H., Dillen J., Subramanian S., Sloan B., Bianchi S., Pinto D., Saliba C., Culap K., Wojcechowskyj J.A., Noack J., Zhou J., Kaiser H., Lee S., Farhat N., Chase A., Montiel-Ruiz M., Dellota E., Park A., Spreafico R., Sahakyan A., Lauron E.J., Czudnochowski N., Cameroni E., Ledoux S., Kawaoka Y., Werts A., Colas C., Soriaga L., Telenti A., Purcell L.A., Hwang S., Snell G., Virgin H.W., Corti D., Hebner C.M.

Publication type: Posted Content

Publication date: 2021-03-10

Cold Spring Harbor Laboratory

DOI: 10.1101/2021.03.09.434607

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Abstract

ABSTRACT

Sotrovimab (VIR-7831) and VIR-7832 are dual action monoclonal antibodies (mAbs) targeting the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sotrovimab and VIR-7832 were derived from a parent antibody (S309) isolated from memory B cells of a 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) survivor. Both mAbs contain an “LS” mutation in the Fc region to prolong serum half-life. In addition, VIR-7832 encodes an Fc GAALIE mutation that has been shown previously to evoke CD8+ T-cells in the context of an in vivo viral respiratory infection. Sotrovimab and VIR-7832 neutralize wild-type and variant pseudotyped viruses and authentic virus in vitro. In addition, they retain activity against monoclonal antibody resistance mutations conferring reduced susceptibility to previously authorized mAbs. The sotrovimab/VIR-7832 epitope continues to be highly conserved among circulating sequences consistent with the high barrier to resistance observed in vitro. Furthermore, both mAbs can recruit effector mechanisms in vitro that may contribute to clinical efficacy via elimination of infected host cells. In vitro studies with these mAbs demonstrated no enhancement of infection. In a Syrian Golden hamster proof-of concept wildtype SARS-CoV-2 infection model, animals treated with sotrovimab had less weight loss, and significantly decreased total viral load and infectious virus levels in the lung compared to a control mAb. Taken together, these data indicate that sotrovimab and VIR-7832 are key agents in the fight against COVID-19.

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Citations by journals

	1 2 3 4 5 6
Viruses	Viruses, 6, 3.37% Viruses 6 publications, 3.37%
Nature	Nature, 6, 3.37% Nature 6 publications, 3.37%
Frontiers in Immunology	Frontiers in Immunology, 5, 2.81% Frontiers in Immunology 5 publications, 2.81%
Science	Science, 5, 2.81% Science 5 publications, 2.81%
Scientific Reports	Scientific Reports, 4, 2.25% Scientific Reports 4 publications, 2.25%
Journal of Biomedical Science	Journal of Biomedical Science, 3, 1.69% Journal of Biomedical Science 3 publications, 1.69%
BMC Infectious Diseases	BMC Infectious Diseases, 3, 1.69% BMC Infectious Diseases 3 publications, 1.69%
Microbiology spectrum	Microbiology spectrum, 3, 1.69% Microbiology spectrum 3 publications, 1.69%
Infection	Infection, 3, 1.69% Infection 3 publications, 1.69%
Infectious Diseases and Therapy	Infectious Diseases and Therapy, 2, 1.12% Infectious Diseases and Therapy 2 publications, 1.12%
Nature Medicine	Nature Medicine, 2, 1.12% Nature Medicine 2 publications, 1.12%
Journal of Clinical Medicine	Journal of Clinical Medicine, 2, 1.12% Journal of Clinical Medicine 2 publications, 1.12%
Clinical Microbiology Reviews	Clinical Microbiology Reviews, 2, 1.12% Clinical Microbiology Reviews 2 publications, 1.12%
International Journal of Biological Macromolecules	International Journal of Biological Macromolecules, 2, 1.12% International Journal of Biological Macromolecules 2 publications, 1.12%
Canadian Journal of Chemistry	Canadian Journal of Chemistry, 1, 0.56% Canadian Journal of Chemistry 1 publication, 0.56%
Journal of Pharmaceutical Innovation	Journal of Pharmaceutical Innovation, 1, 0.56% Journal of Pharmaceutical Innovation 1 publication, 0.56%
Biochemical Society Transactions	Biochemical Society Transactions, 1, 0.56% Biochemical Society Transactions 1 publication, 0.56%
BMJ Open	BMJ Open, 1, 0.56% BMJ Open 1 publication, 0.56%
Nursing	Nursing, 1, 0.56% Nursing 1 publication, 0.56%
Pharmaceuticals	Pharmaceuticals, 1, 0.56% Pharmaceuticals 1 publication, 0.56%
Vaccines	Vaccines, 1, 0.56% Vaccines 1 publication, 0.56%
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 1, 0.56% International Journal of Molecular Sciences 1 publication, 0.56%
Antibodies	Antibodies, 1, 0.56% Antibodies 1 publication, 0.56%
Biomedicines	Biomedicines, 1, 0.56% Biomedicines 1 publication, 0.56%
Microbial Cell Factories	Microbial Cell Factories, 1, 0.56% Microbial Cell Factories 1 publication, 0.56%
Nature Reviews Genetics	Nature Reviews Genetics, 1, 0.56% Nature Reviews Genetics 1 publication, 0.56%
Cell Discovery	Cell Discovery, 1, 0.56% Cell Discovery 1 publication, 0.56%
npj Vaccines	npj Vaccines, 1, 0.56% npj Vaccines 1 publication, 0.56%
Signal Transduction and Targeted Therapy	Signal Transduction and Targeted Therapy, 1, 0.56% Signal Transduction and Targeted Therapy 1 publication, 0.56%
	1 2 3 4 5 6

Citations by publishers

	5 10 15 20 25 30 35 40 45 50
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 46, 25.84% Cold Spring Harbor Laboratory 46 publications, 25.84%
Springer Nature	Springer Nature, 44, 24.72% Springer Nature 44 publications, 24.72%
Elsevier	Elsevier, 20, 11.24% Elsevier 20 publications, 11.24%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 15, 8.43% Multidisciplinary Digital Publishing Institute (MDPI) 15 publications, 8.43%
Wiley	Wiley, 7, 3.93% Wiley 7 publications, 3.93%
American Association for the Advancement of Science (AAAS)	American Association for the Advancement of Science (AAAS), 7, 3.93% American Association for the Advancement of Science (AAAS) 7 publications, 3.93%
American Society for Microbiology	American Society for Microbiology, 7, 3.93% American Society for Microbiology 7 publications, 3.93%
Taylor & Francis	Taylor & Francis, 6, 3.37% Taylor & Francis 6 publications, 3.37%
Frontiers Media S.A.	Frontiers Media S.A., 5, 2.81% Frontiers Media S.A. 5 publications, 2.81%
BMJ	BMJ, 3, 1.69% BMJ 3 publications, 1.69%
American Chemical Society (ACS)	American Chemical Society (ACS), 3, 1.69% American Chemical Society (ACS) 3 publications, 1.69%
Oxford University Press	Oxford University Press, 2, 1.12% Oxford University Press 2 publications, 1.12%
Canadian Science Publishing	Canadian Science Publishing, 1, 0.56% Canadian Science Publishing 1 publication, 0.56%
Portland Press	Portland Press, 1, 0.56% Portland Press 1 publication, 0.56%
Wolters Kluwer Health	Wolters Kluwer Health, 1, 0.56% Wolters Kluwer Health 1 publication, 0.56%
Rockefeller University Press	Rockefeller University Press, 1, 0.56% Rockefeller University Press 1 publication, 0.56%
eLife Sciences Publications	eLife Sciences Publications, 1, 0.56% eLife Sciences Publications 1 publication, 0.56%
Annual Reviews	Annual Reviews, 1, 0.56% Annual Reviews 1 publication, 0.56%
Bentham Science	Bentham Science, 1, 0.56% Bentham Science 1 publication, 0.56%
Public Library of Science (PLoS)	Public Library of Science (PLoS), 1, 0.56% Public Library of Science (PLoS) 1 publication, 0.56%
Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii	Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii, 1, 0.56% Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii 1 publication, 0.56%
	5 10 15 20 25 30 35 40 45 50

We do not take into account publications without a DOI.
Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
Statistics recalculated weekly.

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