@article{00a77d20bced4769b0b26f1b2fd2f384,
title = "A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope",
abstract = "With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here, we developed a panel of neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) that bound the receptor binding domain of the spike protein at distinct epitopes and blocked virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Although several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by ancestral SARS-CoV-2 strains, others induced escape variants in vivo or lost neutralizing activity against emerging strains. One mAb, SARS2-38, potently neutralized all tested SARS-CoV-2 variants of concern and protected mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engaged a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of neutralizing antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants.",
keywords = "SARS-CoV-2, neutralizing antibodies, variants of concern",
author = "VanBlargan, {Laura A.} and Adams, {Lucas J.} and Zhuoming Liu and Chen, {Rita E.} and Pavlo Gilchuk and Saravanan Raju and Smith, {Brittany K.} and Haiyan Zhao and Case, {James Brett} and Winkler, {Emma S.} and Whitener, {Bradley M.} and Lindsay Droit and Aziati, {Ishmael D.} and Bricker, {Traci L.} and Astha Joshi and Shi, {Pei Yong} and Adrian Creanga and Amarendra Pegu and Handley, {Scott A.} and David Wang and Boon, {Adrianus C.M.} and Crowe, {James E.} and Whelan, {Sean P.J.} and Fremont, {Daved H.} and Diamond, {Michael S.}",
note = "Funding Information: This study was supported by contracts and grants from the NIH ( 75N93019C00062 , HHSN272201700060C , 75N93019C00074 , U01 AI151810 , R01 AI118938 , and R01 AI157155 ) and the Defense Advanced Research Project Agency ( HR001117S0019 ). J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. We acknowledge the originating and submitting laboratories who generated and shared genetic sequence data via the GISAID Initiative. We also thank Charles Chiu and Raul Andino for providing the B.1.429 isolate and Barney Graham for cell lines and experimental advice. The Graphical Abstract was created with BioRender. Funding Information: M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, and Carnival Corporation and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. Some of the mAbs described in this study have been licensed by Washington University to Bio X Cell. D.H.F is a founder of Courier Therapeutics and has received funding support in a sponsored research agreement from Emergent BioSolutions. J.E.C. has served as a consultant for Eli Lilly and Luna Biologics, is a member of the Scientific Advisory Boards of CompuVax and Meissa Vaccines, and is the founder of IDBiologics. The Crowe laboratory at Vanderbilt University Medical Center has received sponsored research agreements from AstraZeneca and IDBiologics. The Boon laboratory has received funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences, AbbVie, and Nano Targeting & Therapy Biopharma. Funding Information: This study was supported by contracts and grants from the NIH (75N93019C00062, HHSN272201700060C, 75N93019C00074, U01 AI151810, R01 AI118938, and R01 AI157155) and the Defense Advanced Research Project Agency (HR001117S0019). J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. We acknowledge the originating and submitting laboratories who generated and shared genetic sequence data via the GISAID Initiative. We also thank Charles Chiu and Raul Andino for providing the B.1.429 isolate and Barney Graham for cell lines and experimental advice. The Graphical Abstract was created with BioRender. Conceptualization and methodology, L.A.V. M.S.D. L.J.A. D.H.F. Z.L. and S.P.J.W; investigation, L.A.V. L.J.A. Z.L. R.E.C. P.G. S.R. B.K.S. J.B.C. B.M.W. L.D. I.D.A. T.L.B. and A.J.; formal analysis, L.J.A. and S.A.H.; key reagents, E.S.W. H.Z. P.-Y.S. A.P. and A.C.; supervision and funding, M.S.D. D.H.F. D.W. A.C.M.B. J.E.C. and S.P.J.W; writing ? original draft, L.A.V. L.J.A. and M.S.D.; writing ? review and editing, all authors. M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, and Carnival Corporation and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. Some of the mAbs described in this study have been licensed by Washington University to Bio X Cell. D.H.F is a founder of Courier Therapeutics and has received funding support in a sponsored research agreement from Emergent BioSolutions. J.E.C. has served as a consultant for Eli Lilly and Luna Biologics, is a member of the Scientific Advisory Boards of CompuVax and Meissa Vaccines, and is the founder of IDBiologics. The Crowe laboratory at Vanderbilt University Medical Center has received sponsored research agreements from AstraZeneca and IDBiologics. The Boon laboratory has received funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences, AbbVie, and Nano Targeting & Therapy Biopharma. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = oct,
day = "12",
doi = "10.1016/j.immuni.2021.08.016",
language = "English",
volume = "54",
pages = "2399--2416.e6",
journal = "Immunity",
issn = "1074-7613",
number = "10",
}