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Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant

Carl Graham, Jeffrey Seow, Isabella Huettner and 26 more

Immunity · 2021 · CC BY

doi:10.1016/j.immuni.2021.03.023

Abstract

Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. To understand how these mutations affect Spike antigenicity, we isolated and characterized >100 monoclonal antibodies targeting epitopes on RBD, NTD, and S2 from SARS-CoV-2-infected individuals. Approximately 45% showed neutralizing activity, of which ∼20% were NTD specific. NTD-specific antibodies formed two distinct groups: the first was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Mutations present in B.1.1.7 Spike frequently conferred neutralization resistance to NTD-specific antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes should be considered when investigating antigenic drift in emerging variants.

References 86

1.
SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma · 2021
No notice
2.
Andreano E., Nicastri E., Paciello I., Pileri P., Manganaro N., Piccini G., Manenti A., Pantano E., Kabanova A., Troisi M. Extremely potent human monoclonal antibodies from COVID-19 convalescent patients. Cell. 2021.
Not in our library10.1016/j.cell.2021.02.035
3.
Aricescu A.R., Lu W., Jones E.Y. A time- and cost-efficient system for high-level protein production in mammalian cells. Acta Crystallogr. D Biol. Crystallogr. 2006;62:1243-1250.
Not in our library10.1107/s0907444906029799
4.
Avanzato V.A., Matson M.J., Seifert S.N., Pryce R., Williamson B.N., Anzick S.L., Barbian K., Judson S.D., Fischer E.R., Martens C. Case Study: Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer. Cell. 2020;183:1901-1912.e1909.
Not in our library10.1016/j.cell.2020.10.049
5.
Barnes C.O., Jette C.A., Abernathy M.E., Dam K.A., Esswein S.R., Gristick H.B., Malyutin A.G., Sharaf N.G., Huey-Tubman K.E., Lee Y.E. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature. 2020;588:682-687.
Not in our library10.1038/s41586-020-2852-1
6.
Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals · 2020
No notice
7.
Bournazos S., Corti D., Virgin H.W., Ravetch J.V. Fc-optimized antibodies elicit CD8 immunity to viral respiratory infection. Nature. 2020;588:485-490.
Not in our library10.1038/s41586-020-2838-z
8.
Briney B., Inderbitzin A., Joyce C., Burton D.R. Commonality despite exceptional diversity in the baseline human antibody repertoire. Nature. 2019;566:393-397.
Not in our library10.1038/s41586-019-0879-y
9.
Brochet X., Lefranc M.P., Giudicelli V. IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucleic Acids Res. 2008;36:W503-8.
Not in our library10.1093/nar/gkn316
10.
Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability · 2020
No notice
11.
Carter M.J., Fish M., Jennings A., Doores K.J., Wellman P., Seow J., Acors S., Graham C., Timms E., Kenny J. Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection. Nat. Med. 2020;26:1701-1707.
Not in our library10.1038/s41591-020-1054-6
12.
Characterisation W.H.O.W.G.C., WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect. Dis. 2020;20:e192-e197.
Not in our library10.1016/s1473-3099(20)30483-7
13.
Chen R.E., Zhang X., Case J.B., Winkler E.S., Liu Y., VanBlargan L.A., Liu J., Errico J.M., Xie X., Suryadevara N. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 2021.
Not in our library10.1038/s41591-021-01294-w
14.
A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2 · 2020
No notice
15.
Choi B., Choudhary M.C., Regan J., Sparks J.A., Padera R.F., Qiu X., Solomon I.H., Kuo H.H., Boucau J., Bowman K. Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host. N. Engl. J. Med. 2020;383:2291-2293.
Not in our library10.1056/nejmc2031364
16.
Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies · 2021
Corrected
17.
Dynamics of Neutralizing Antibody Titers in the Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection · 2020
No notice
18.
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection · 2021
No notice
19.
Dixon E.V. Mechanisms of immunoglobulin deactivation by Streptococcus pyogenes. 2014.
Not in our library
20.
Doores K.J., Burton D.R. Variable loop glycan dependency of the broad and potent HIV-1-neutralizing antibodies PG9 and PG16. J. Virol. 2010;84:10510-10521.
Not in our library10.1128/jvi.00552-10
21.
Doores K.J., Kong L., Krumm S.A., Le K.M., Sok D., Laserson U., Garces F., Poignard P., Wilson I.A., Burton D.R. Two classes of broadly neutralizing antibodies within a single lineage directed to the high-mannose patch of HIV envelope. J. Virol. 2015;89:1105-1118.
Not in our library10.1128/jvi.02905-14
22.
Edara V.V., Floyd K., Lai L., Gardner M., Hudson W., Piantadosi A., Waggoner J.J., Babiker A., Ahmed R., Xie X. Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant. medRxiv. 2021.
Not in our library
23.
Greaney A.J., Loes A.N., Crawford K.H.D., Starr T.N., Malone K.D., Chu H.Y., Bloom J.D. Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host Microbe. 2021;29:463-476.e6.
Not in our library10.1016/j.chom.2021.02.003
24.
Grehan K., Ferrara F., Temperton N. An optimised method for the production of MERS-CoV spike expressing viral pseudotypes. MethodsX. 2015;2:379-384.
Not in our library10.1016/j.mex.2015.09.003
25.
Gu Z., Eils R., Schlesner M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics. 2016;32:2847-2849.
Not in our library10.1093/bioinformatics/btw313
26.
SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike · 2021
Not checked
27.
Howarth M., Liu W., Puthenveetil S., Zheng Y., Marshall L.F., Schmidt M.M., Wittrup K.D., Bawendi M.G., Ting A.Y. Monovalent, reduced-size quantum dots for imaging receptors on living cells. Nat. Methods. 2008;5:397-399.
Not in our library10.1038/nmeth.1206
28.
Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses · 2020
Corrected
29.
Kemp S.A., Collier D.A., Datir R.P., Ferreira I.A.T.M., Gayed S., Jahun A., Hosmillo M., Rees-Spear C., Mlcochova P., Lumb I.U., CITIID-NIHR BioResource COVID-19 Collaboration, COVID-19 Genomics UK (COG-UK) Consortium. SARS-CoV-2 evolution during treatment of chronic infection. Nature. 2021.
Not in our library10.1038/s41586-021-03291-y
30.
Kim S.I., Noh J., Kim S., Choi Y., Yoo D.K., Lee Y., Lee H., Jung J., Kang C.K., Song K.H. Stereotypic neutralizing VH antibodies against SARS-CoV-2 spike protein receptor binding domain in patients with COVID-19 and healthy individuals. Sci. Transl. Med. 2021;13:eabd6990.
Not in our library10.1126/scitranslmed.abd6990
31.
Laing A.G., Lorenc A., Del Molino Del Barrio I., Das A., Fish M., Monin L., Muñoz-Ruiz M., McKenzie D.R., Hayday T.S., Francos-Quijorna I. A dynamic COVID-19 immune signature includes associations with poor prognosis. Nat. Med. 2020;26:1623-1635.
Not in our library10.1038/s41591-020-1038-6
32.
A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity · 2021
No notice
33.
Li Q., Wu J., Nie J., Zhang L., Hao H., Liu S., Zhao C., Zhang Q., Liu H., Nie L. The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity. Cell. 2020;182:1284-1294.e1289.
Not in our library10.1016/j.cell.2020.07.012
34.
Li W., Chen C., Drelich A., Martinez D.R., Gralinski L.E., Sun Z., Schäfer A., Kulkarni S.S., Liu X., Leist S.R. Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection. Proc. Natl. Acad. Sci. USA. 2020;117:29832-29838.
Not in our library10.1073/pnas.2010197117
35.
Cross-Neutralization of a SARS-CoV-2 Antibody to a Functionally Conserved Site Is Mediated by Avidity · 2020
No notice
36.
Liu L., Wang P., Nair M.S., Yu J., Rapp M., Wang Q., Luo Y., Chan J.F., Sahi V., Figueroa A. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature. 2020;584:450-456.
Not in our library10.1038/s41586-020-2571-7
37.
Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., Wang W., Song H., Huang B., Zhu N. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565-574.
Not in our library10.1016/s0140-6736(20)30251-8
38.
McCallum M., Marco A., Lempp F., Tortorici M.A., Pinto D., Walls A.C., Beltramello M., Chen A., Liu Z., Zatta F. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell. 2021.
Not in our library10.1016/j.cell.2021.03.028
39.
Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape · 2021
No notice
40.
Muecksch F., Wise H., Batchelor B., Squires M., Semple E., Richardson C., McGuire J., Clearly S., Furrie E., Greig N. Longitudinal analysis of serology and neutralizing antibody levels in COVID19 convalescents. J. Infect. Dis. 2020.
Not in our library10.1093/infdis/jiaa659
41.
Severe Acute Respiratory Syndrome Coronavirus 2−Specific Antibody Responses in Coronavirus Disease Patients · 2020
No notice
42.
Piccoli L., Park Y.J., Tortorici M.A., Czudnochowski N., Walls A.C., Beltramello M., Silacci-Fregni C., Pinto D., Rosen L.E., Bowen J.E. Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology. Cell. 2020;183:1024-1042.e1021.
Not in our library10.1016/j.cell.2020.09.037
43.
Pickering S., Betancor G., Galão R.P., Merrick B., Signell A.W., Wilson H.D., Kia Ik M.T., Seow J., Graham C., Acors S. Comparative assessment of multiple COVID-19 serological technologies supports continued evaluation of point-of-care lateral flow assays in hospital and community healthcare settings. PLoS Pathog. 2020;16:e1008817.
Not in our library10.1371/journal.ppat.1008817
44.
Pinto D., Park Y.J., Beltramello M., Walls A.C., Tortorici M.A., Bianchi S., Jaconi S., Culap K., Zatta F., De Marco A. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature. 2020;583:290-295.
Not in our library10.1038/s41586-020-2349-y
45.
Cross-Sectional Evaluation of Humoral Responses against SARS-CoV-2 Spike · 2020
Not checked
46.
Rambaut A., Loman N., Pybus O., Barclay W., Barrett J., Carabelli A., Connor T., Peacock T., Robertson D.L., Volz E. Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations. 2020.
Not in our library
47.
The effect of spike mutations on SARS-CoV-2 neutralization · 2021
No notice
48.
Robbiani D.F., Gaebler C., Muecksch F., Lorenzi J.C.C., Wang Z., Cho A., Agudelo M., Barnes C.O., Gazumyan A., Finkin S. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature. 2020;584:437-442.
Not in our library10.1038/s41586-020-2456-9
49.
Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model · 2020
No notice
50.
SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity · 2021
No notice
51.
Scheid J.F., Mouquet H., Feldhahn N., Seaman M.S., Velinzon K., Pietzsch J., Ott R.G., Anthony R.M., Zebroski H., Hurley A. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature. 2009;458:636-640.
Not in our library10.1038/nature07930
52.
Seow J., Graham C., Merrick B., Acors S., Pickering S., Steel K.J.A., Hemmings O., O’Byrne A., Kouphou N., Galao R.P. Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans. Nat. Microbiol. 2020;5:1598-1607.
Not in our library10.1038/s41564-020-00813-8
53.
Seydoux E., Homad L.J., MacCamy A.J., Parks K.R., Hurlburt N.K., Jennewein M.F., Akins N.R., Stuart A.B., Wan Y.H., Feng J. Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation. Immunity. 2020;53:98-105.e105.
Not in our library10.1016/j.immuni.2020.06.001
54.
Shen X., Tang H., McDanal C., Wagh K., Fischer W., Theiler J., Yoon H., Li D., Haynes B.F., Sanders K.O. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines. Cell Host Microbe. 2021.
Not in our library10.1016/j.chom.2021.03.002
55.
Prospective mapping of viral mutations that escape antibodies used to treat COVID-19 · 2021
No notice
56.
Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera · 2021
No notice
57.
Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants · 2006
No notice
58.
Thompson C.P., Grayson N.E., Paton R.S., Bolton J.S., Lourenço J., Penman B.S., Lee L.N., Odon V., Mongkolsapaya J., Chinnakannan S., ISARIC4C Investigators. Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020. Euro Surveill. 2020;25:2000685.
Not in our library10.2807/1560-7917.es.2020.25.42.2000685
59.
Tiller T., Meffre E., Yurasov S., Tsuiji M., Nussenzweig M.C., Wardemann H. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J. Immunol. Methods. 2008;329:112-124.
Not in our library10.1016/j.jim.2007.09.017
60.
Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms · 2020
No notice
61.
van den Brink E.N., Ter Meulen J., Cox F., Jongeneelen M.A., Thijsse A., Throsby M., Marissen W.E., Rood P.M., Bakker A.B., Gelderblom H.R. Molecular and biological characterization of human monoclonal antibodies binding to the spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus. J. Virol. 2005;79:1635-1644.
Not in our library10.1128/jvi.79.3.1635-1644.2005
62.
von Boehmer L., Liu C., Ackerman S., Gitlin A.D., Wang Q., Gazumyan A., Nussenzweig M.C. Sequencing and cloning of antigen-specific antibodies from mouse memory B cells. Nat. Protoc. 2016;11:1908-1923.
Not in our library10.1038/nprot.2016.102
63.
Walls A.C., Park Y.J., Tortorici M.A., Wall A., McGuire A.T., Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020;183:1735.
Not in our library10.1016/j.cell.2020.11.032
64.
A human monoclonal antibody blocking SARS-CoV-2 infection · 2020
Corrected
65.
Wang P., Nair M.S., Liu L., Iketani S., Luo Y., Guo Y., Wang M., Yu J., Zhang B., Kwong P.D. Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7. Nature. 2021.
Not in our library10.1038/s41586-021-03398-2
66.
Site-specific glycan analysis of the SARS-CoV-2 spike · 2020
No notice
67.
Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants · 2020
No notice
68.
Weissman D., Alameh M.G., de Silva T., Collini P., Hornsby H., Brown R., LaBranche C.C., Edwards R.J., Sutherland L., Santra S. D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization. Cell Host Microbe. 2020;29(1):23-31.e4.
Not in our library10.1016/j.chom.2020.11.012
69.
Wibmer C.K., Ayres F., Hermanus T., Madzivhandila M., Kgagudi P., Oosthuysen B., Lambson B.E., de Oliveira T., Vermeulen M., van der Berg K. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. Nat. Med. 2021.
Not in our library10.1038/s41591-021-01285-x
70.
Wickham Hadley. ggplot2: Elegant Graphics for Data Analysis. 2016.
Not in our library
71.
The Polybasic Cleavage Site in SARS-CoV-2 Spike Modulates Viral Sensitivity to Type I Interferon and IFITM2 · 2021
No notice
72.
Wise J. Covid-19: The E484K mutation and the risks it poses. BMJ. 2021;372:n359.
Not in our library10.1136/bmj.n359
73.
Wrapp D., Wang N., Corbett K.S., Goldsmith J.A., Hsieh C.L., Abiona O., Graham B.S., McLellan J.S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367:1260-1263.
Not in our library10.1126/science.abb2507
74.
An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain · 2020
No notice
75.
A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2 · 2020
No notice
76.
Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration · 2020
No notice
77.
Yao H., Song Y., Chen Y., Wu N., Xu J., Sun C., Zhang J., Weng T., Zhang Z., Wu Z. Molecular Architecture of the SARS-CoV-2 Virus. Cell. 2020;183:730-738.e713.
Not in our library10.1016/j.cell.2020.09.018
78.
Structural basis of a shared antibody response to SARS-CoV-2 · 2020
No notice
79.
Recognition of the SARS-CoV-2 receptor binding domain by neutralizing antibodies · 2021
No notice
80.
Yuan M., Wu N.C., Zhu X., Lee C.D., So R.T.Y., Lv H., Mok C.K.P., Wilson I.A. A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV. Science. 2020;368:630-633.
Not in our library10.1126/science.abb7269
81.
Yurkovetskiy L., Wang X., Pascal K.E., Tomkins-Tinch C., Nyalile T.P., Wang Y., Baum A., Diehl W.E., Dauphin A., Carbone C. Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant. Cell. 2020;183:739-751.e738.
Not in our library10.1016/j.cell.2020.09.032
82.
Zhou T., Tsybovsky Y., Gorman J., Rapp M., Cerutti G., Chuang G.Y., Katsamba P.S., Sampson J.M., Schon A., Bimela J. Cryo-EM Structures of SARS-CoV-2 Spike without and with ACE2 Reveal a pH-Dependent Switch to Mediate Endosomal Positioning of Receptor-Binding Domains. Cell Host Microbe. 2020;28:867-879.e865.
Not in our library10.1016/j.chom.2020.11.004
83.
Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera · 2021
No notice
84.
Zohar T., Loos C., Fischinger S., Atyeo C., Wang C., Slein M.D., Burke J., Yu J., Feldman J., Hauser B.M. Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality. Cell. 2020;183:1508-1519 e1512.
Not in our library10.1016/j.cell.2020.10.052
85.
Zost S.J., Gilchuk P., Case J.B., Binshtein E., Chen R.E., Nkolola J.P., Schäfer A., Reidy J.X., Trivette A., Nargi R.S. Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature. 2020;584:443-449.
Not in our library10.1038/s41586-020-2548-6
86.
Zufferey R., Nagy D., Mandel R.J., Naldini L., Trono D. Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat. Biotechnol. 1997;15:871-875.
Not in our library10.1038/nbt0997-871

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