Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects

Jennewein, Madeleine F.; MacCamy, Anna J.; Akins, Nicholas R.; Feng, Junli; Homad, Leah J.; Hurlburt, Nicholas K.; Seydoux, Emilie; Wan, Yu-Hsin; Stuart, Andrew B.; Edara, Venkata Viswanadh; Floyd, Katharine; Vanderheiden, Abigail; Mascola, John R.; Doria-Rose, Nicole; Wang, Lingshu; Yang, Eun Sung; Chu, Helen Y.; Torres, Jonathan L.; Ozorowski, Gabriel; Ward, Andrew B.; Whaley, Rachael E.; Cohen, Kristen W.; Pancera, Marie; McElrath, M. Juliana; Englund, Janet A.; Finzi, Andrés; Suthar, Mehul S.; McGuire, Andrew T.; Stamatatos, Leonidas

doi:10.1016/j.celrep.2021.109353

Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects

Journal Article · Tue Jun 22 00:00:00 EDT 2021 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2021.109353· OSTI ID:1815023

Jennewein, Madeleine F. ^[1]; MacCamy, Anna J. ^[1]; Akins, Nicholas R. ^[1]; Feng, Junli ^[1]; Homad, Leah J. ^[1]; Hurlburt, Nicholas K. ^[1]; Seydoux, Emilie ^[1]; Wan, Yu-Hsin ^[1]; Stuart, Andrew B. ^[1]; Edara, Venkata Viswanadh ^[2]; Floyd, Katharine ^[2]; Vanderheiden, Abigail ^[2]; Mascola, John R. ^[3]; Doria-Rose, Nicole ^[3]; Wang, Lingshu ^[3]; Yang, Eun Sung ^[3]; Chu, Helen Y. ^[4]; Torres, Jonathan L. ^[5]; Ozorowski, Gabriel ^[5]; Ward, Andrew B. ^[5] more »

Fred Hutchinson Cancer Research Center, Seattle, WA (United States)
Emory University School of Medicine, Atlanta, GA (United States)
National Institutes of Health (NIH), Bethesda, MD (United States). Vaccine Research Center
Univ. of Washington, Seattle, WA (United States)
The Scripps Research Inst., La Jolla, CA (United States)
Fred Hutchinson Cancer Research Center, Seattle, WA (United States); National Institutes of Health (NIH), Bethesda, MD (United States). Vaccine Research Center
Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)
Univ. of Washington, Seattle, WA (United States); Seattle Children's Research Institute, Seattle, WA (United States)
Univ. of Montreal, QC (Canada)

SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: Bill and Melinda Gates Foundation; Club Foundation; Fondation du CHUM; Fred Hutch COVID-19 Research Fund; Ministry of Economy, Innovation and Energy, Canada; National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1815023

Alternate ID(s):: OSTI ID: 1818353

Journal Information:: Cell Reports, Journal Name: Cell Reports Journal Issue: 2 Vol. 36; ISSN 2211-1247

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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60 APPLIED LIFE SCIENCES
B.1.351
CV3-25
NTD
RBD
S2 subunit
SARS-CoV-1
SARS-CoV-2
monoclonal antibodies
neutralization

Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19+ subjects

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