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Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies
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Abstract
and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.
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In the citing paper
“Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection7,8.”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [8]
In the citing paper
“As expected, plasma neutralizing activity was directly correlated to anti-S and -RBD binding titers in ELISAs7,8 (Fig. 1c, d, and Extended Data Fig. 2a–d).”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [8]
In the citing paper
“A475V is resistant to class 1 antibodies (structurally defined as described29); E484K and Q493R are resistant to class 2 antibodies7,8,12,13,29,30,32,33; while R346S, N439K, and N440K are resistant to class 3 antibodies7,8,12,13,29,33.”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [8]
In the citing paper
“In addition, antibodies that share the same combination of IGHV and IGLV genes in vaccinees comprised 39% of all the clonal sequences (Extended Data Fig. 4b) and 59% when combined with naturally infected individuals7,8 (Fig. 2f), and some of these antibodies were nearly identical (Extended Data Table 3 and 4).”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [8]
In the citing paper
“Class 1 and 2 antibodies are among the most potent and also the most abundant antibodies7,8,21,22,25,39.”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [8]
In the citing paper
“Consistent with the plasma neutralization results, the geometric mean neutralization half-maximal inhibitory concentration of the Pfizer-BioNTech and Moderna vaccinee antibodies were not significantly different from each other or to antibody collections obtained from naturally infected individuals 1.3 or 6.2 months after infection (Fig. 3a and 7,8).”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [8]
In the citing paper
“In anti-RBD ELISAs the mean half-maximal effective concentration (EC50) was higher than that observed in infected individuals after 6.2 months but not significantly different from antibodies obtained 1.3 months after infection (Extended Data Fig. 6a, and Table 5 and 7,8).”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [8]
In the citing paper
“Numerous neutralizing anti-RBD monoclonal antibodies (mAbs) have been characterized, the most potent of which block the RBD-ACE2 interaction (16, 17, 22–24, 32–37).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [32]
In the citing paper
“Antibodies binding to the RBD can potently block attachment of the virus to ACE2 and thereby neutralize the virus”
From SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2 (2021) · cites this paper as Barnes et al., 2020
In the citing paper
“Their engagement with the RBD is dictated by CDR-H1 and CDR-H2, while the CDR-H3 is characteristically short and makes rather few interactions”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Barnes et al., 2020
In the citing paper
“A number of public antibody responses have been reported for SARS-CoV-2, principal among these being VH3–53/VH3–66 and VH1–58 (VH3–30 is also found, but the antibodies are not potent neutralizers) (Yuan et al., 2020; Barnes et al., 2020; Dejnirattisai et al., 2021).”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Barnes et al., 2020
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Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies
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Convergent Antibody Responses to SARS-CoV-2 in Convalescent Individuals
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Self-citationEvolution of antibody immunity to SARS-CoV-2
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Self-citationSARS-CoV-2 neutralizing antibody structures inform therapeutic strategies
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Self-citationEscape from neutralizing antibodies by SARS-CoV-2 spike protein variants
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Metadata
- Authors
- Barnes, C. O., West, A. P., Huey-Tubman, K. E., Hoffmann, M. A. G., Sharaf, N. G., Hoffman, P. R., Koranda, N., Gristick, H. B., Gaebler, C., Muecksch, F., Lorenzi, J. C. C., Finkin, S., Hägglöf, T., Hurley, A., Millard, K. G., Weisblum, Y., Schmidt, F., Hatziioannou, T., Bieniasz, P. D., Caskey, M., Robbiani, D. F., Nussenzweig, M. C., & Bjorkman, P. J.
- Affiliations
- California Institute of Technology (US)
- Rockefeller University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Nussenzweig, Michel C.
- ORCID
- Barnes, Christopher O.
- West, Anthony P.
- Hoffmann, Magnus A.G.
- Sharaf, Naima G.
- Hoffman, Pauline R.
- Koranda, Nicholas
- Gristick, Harry B.
- Gaebler, Christian
- Muecksch, Frauke
- Lorenzi, Julio C. Cetrulo
- Finkin, Shlomo
- Hägglöf, Thomas
- Hurley, Arlene
- Millard, Katrina G.
- Weisblum, Yiska
- Schmidt, Fabian
- Bieniasz, Paul D.
- Caskey, Marina
- Robbiani, Davide F.
- Nussenzweig, Michel C.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 182
- Issue
- 4
- Pages
- 828-842.e16
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7311918
- OpenAlex
- W3036607916
- Cited by
- 795
- References
- 109
- Citations by year
- 2026: 34 · 2025: 49 · 2024: 50 · 2023: 84 · 2022: 151 · 2021: 319 · 2020: 107
- FWCI
- 21.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by-nc-nd)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- National Center for Advancing Translational Sciences (UL1 TR001866)
- Burroughs Wellcome Fund
- Howard Hughes Medical Institute
- Basic Energy Sciences (DE-AC02-76SF00515)
- National Institute of General Medical Sciences (P41GM103393, 2U19AI111825, P50 8 P50 AI150464-13, P01-AI138938-S1)
- Bill and Melinda Gates Foundation (INV-002143)
- Office of Science
- Biological and Environmental Research
- U.S. Department of Energy
- Beckman Institute, California Institute of Technology
- George Mason University
- California Institute of Technology
- National Institutes of Health
- Rockefeller University
- Icahn School of Medicine at Mount Sinai
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Keywords
- SARS-CoV-2 spike protein, human antibodies, neutralizing antibodies, ACE2 binding, IgG, spike protein mutations, vaccine-elicited antibodies, antibody structure
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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