Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants.

Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE

Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-

Antibodies, Neutralizing/*immunology ; Antibodies, Viral/*immunology ; COVID-19/*immunology ; SARS-CoV-2/*immunology ; SARS-CoV-2/*pathogenicity ; Spike Glycoprotein, Coronavirus/*immunology; Angiotensin-Converting Enzyme 2/antagonists & inhibitors ; Angiotensin-Converting Enzyme 2/metabolism ; Antibodies, Neutralizing/chemistry ; Antibodies, Neutralizing/metabolism ; Antibodies, Viral/chemistry ; Antibodies, Viral/metabolism ; Antibody Affinity ; Antigen-Antibody Reactions ; COVID-19/virology ; Humans ; Immune Evasion ; Immunoglobulin Fab Fragments/immunology ; Immunoglobulin Fab Fragments/metabolism ; Mutation ; Neutralization Tests ; Protein Domains ; Receptors, Coronavirus/antagonists & inhibitors ; Receptors, Coronavirus/metabolism ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism

The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain-targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC 50 ) 0.3 to 11.1 nanograms per milliliter; IC 80 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Update of: bioRxiv. 2021 Mar 01:2021.02.25.432969. doi: 10.1101/2021.02.25.432969. (PMID: 33655252)

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F32 AI152296 United States AI NIAID NIH HHS; T32 AI007151 United States AI NIAID NIH HHS; R01 AI157155 United States AI NIAID NIH HHS; HHSN261200800001C United States CA NCI NIH HHS; HHSN261200800001E United States CA NCI NIH HHS

0 (Antibodies, Neutralizing)
0 (Antibodies, Viral)
0 (Immunoglobulin Fab Fragments)
0 (Receptors, Coronavirus)
0 (Spike Glycoprotein, Coronavirus)
0 (spike protein, SARS-CoV-2)
EC 3.4.17.23 (ACE2 protein, human)
EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)

Date Created: 20210702 Date Completed: 20210820 Latest Revision: 20240923

20240923

PMC9269068

10.1126/science.abh1766

34210892