Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition

Kevin J. Kramer; Nicole V. Johnson; Andrea R. Shiakolas; Naveenchandra Suryadevara; Sivakumar Periasamy; Nagarajan Raju; Jazmean K. Williams; Daniel Wrapp; Seth J. Zost; Lauren M. Walker; Steven C. Wall; Clinton M. Holt; Ching Lin Hsieh; Rachel E. Sutton; Ariana Paulo; Rachel S. Nargi; Edgar Davidson; Benjamin J. Doranz; James E. Crowe; Alexander Bukreyev; Robert H. Carnahan; Jason S. McLellan; Ivelin S. Georgiev

doi:10.1016/j.celrep.2021.109784

Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition

Kevin J. Kramer, Nicole V. Johnson, Andrea R. Shiakolas, Naveenchandra Suryadevara, Sivakumar Periasamy, Nagarajan Raju, Jazmean K. Williams, Daniel Wrapp, Seth J. Zost, Lauren M. Walker, Steven C. Wall, Clinton M. Holt, Ching Lin Hsieh, Rachel E. Sutton, Ariana Paulo, Rachel S. Nargi, Edgar Davidson, Benjamin J. Doranz, James E. Crowe, Alexander BukreyevRobert H. Carnahan, Jason S. McLellan, Ivelin S. Georgiev

Pathology

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of coronavirus disease (COVID-19). Therefore, the need for ongoing discovery efforts to identify broadly reactive monoclonal antibodies to SARS-CoV-2 is of utmost importance. Here, we report a panel of SARS-CoV-2 antibodies isolated using the linking B cell receptor to antigen specificity through sequencing (LIBRA-seq) technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 shows potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryoelectron microscopy (cryo-EM) structure of 54042-4 in complex with the SARS-CoV-2 spike reveals an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses uncommon genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings provide motivation for the development of 54042-4 as a lead candidate to counteract current and future SARS-CoV-2 VOCs.

Original language	English (US)
Article number	109784
Journal	Cell Reports
Volume	37
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2021.109784
State	Published - Oct 5 2021

Keywords

COVID-19
Delta variant
LIBRA-seq
SARS-CoV-2
antibody discovery
cryo-EM
monoclonal antibodies biology

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2021.109784

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Kramer, K. J., Johnson, N. V., Shiakolas, A. R., Suryadevara, N., Periasamy, S., Raju, N., Williams, J. K., Wrapp, D., Zost, S. J., Walker, L. M., Wall, S. C., Holt, C. M., Hsieh, C. L., Sutton, R. E., Paulo, A., Nargi, R. S., Davidson, E., Doranz, B. J., Crowe, J. E., ... Georgiev, I. S. (2021). Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition. Cell Reports, 37(1), Article 109784. https://doi.org/10.1016/j.celrep.2021.109784

Kramer, KJ, Johnson, NV, Shiakolas, AR, Suryadevara, N, Periasamy, S, Raju, N, Williams, JK, Wrapp, D, Zost, SJ, Walker, LM, Wall, SC, Holt, CM, Hsieh, CL, Sutton, RE, Paulo, A, Nargi, RS, Davidson, E, Doranz, BJ, Crowe, JE, Bukreyev, A, Carnahan, RH, McLellan, JS & Georgiev, IS 2021, 'Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition', Cell Reports, vol. 37, no. 1, 109784. https://doi.org/10.1016/j.celrep.2021.109784

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title = "Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition",

abstract = "The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of coronavirus disease (COVID-19). Therefore, the need for ongoing discovery efforts to identify broadly reactive monoclonal antibodies to SARS-CoV-2 is of utmost importance. Here, we report a panel of SARS-CoV-2 antibodies isolated using the linking B cell receptor to antigen specificity through sequencing (LIBRA-seq) technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 shows potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryoelectron microscopy (cryo-EM) structure of 54042-4 in complex with the SARS-CoV-2 spike reveals an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses uncommon genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings provide motivation for the development of 54042-4 as a lead candidate to counteract current and future SARS-CoV-2 VOCs.",

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AU - Suryadevara, Naveenchandra

AU - Periasamy, Sivakumar

AU - Raju, Nagarajan

AU - Williams, Jazmean K.

AU - Wrapp, Daniel

AU - Zost, Seth J.

AU - Walker, Lauren M.

AU - Wall, Steven C.

AU - Holt, Clinton M.

AU - Hsieh, Ching Lin

AU - Sutton, Rachel E.

AU - Paulo, Ariana

AU - Nargi, Rachel S.

AU - Davidson, Edgar

AU - Doranz, Benjamin J.

AU - Crowe, James E.

AU - Bukreyev, Alexander

AU - Carnahan, Robert H.

AU - McLellan, Jason S.

AU - Georgiev, Ivelin S.

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Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition

Abstract

Keywords

ASJC Scopus subject areas

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