SARS-CoV-2 variants show resistance to neutralization by many monoclonal and serum-derived polyclonal antibodies

  1. Diamond, Michael
  2. Chen, Rita
  3. XIE, XUPING ORCID logo
  4. Case, James ORCID logo
  5. Zhang, Xianwen
  6. VanBlargan, Laura
  7. Liu, Yang
  8. Liu, Jianying
  9. Errico, John
  10. Winkler, Emma
  11. Suryadevara, Naveenchandra
  12. Tahan, Stephen
  13. Turner, Jackson
  14. Kim, Wooseob ORCID logo
  15. Schmitz, Aaron ORCID logo
  16. Thapa, Mahima
  17. Wang, David
  18. Boon, Andrianus
  19. Pinto, Dora
  20. Presti, Rachel
  21. O’Halloran, Jane
  22. Kim, Alfred
  23. Deepak, Parakkal
  24. Fremont, Daved ORCID logo
  25. Corti, Davide ORCID logo
  26. Virgin, Herbert ORCID logo
  27. Crowe, James ORCID logo
  28. Droit, Lindsay
  29. Ellebedy, Ali ORCID logo
  30. Shi, Pei-Yong ORCID logo
  31. Gilchuk, Pavlo

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WeightNameValue
1000 Titel
  • SARS-CoV-2 variants show resistance to neutralization by many monoclonal and serum-derived polyclonal antibodies
1000 Autor/in
  1. Diamond, Michael |
  2. Chen, Rita |
  3. XIE, XUPING |
  4. Case, James |
  5. Zhang, Xianwen |
  6. VanBlargan, Laura |
  7. Liu, Yang |
  8. Liu, Jianying |
  9. Errico, John |
  10. Winkler, Emma |
  11. Suryadevara, Naveenchandra |
  12. Tahan, Stephen |
  13. Turner, Jackson |
  14. Kim, Wooseob |
  15. Schmitz, Aaron |
  16. Thapa, Mahima |
  17. Wang, David |
  18. Boon, Andrianus |
  19. Pinto, Dora |
  20. Presti, Rachel |
  21. O’Halloran, Jane |
  22. Kim, Alfred |
  23. Deepak, Parakkal |
  24. Fremont, Daved |
  25. Corti, Davide |
  26. Virgin, Herbert |
  27. Crowe, James |
  28. Droit, Lindsay |
  29. Ellebedy, Ali |
  30. Shi, Pei-Yong |
  31. Gilchuk, Pavlo |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-02-10
1000 Erschienen in
1000 Quellenangabe
  • Version 1
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.21203/rs.3.rs-228079/v1 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885928 |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic infecting more than 106 million people and causing 2.3 million deaths. The rapid deployment of antibody-based countermeasures has provided hope for curtailing disease and ending the pandemic1. However, the emergence of rapidly-spreading SARS-CoV-2 variants in the United Kingdom (B.1.1.7), South Africa (B.1.351), and elsewhere with mutations in the spike protein has raised concern for escape from neutralizing antibody responses and loss of vaccine efficacy based on preliminary data with pseudoviruses2-4. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera, and human sera from recipients of the Pfizer-BioNTech (BNT162b2) mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, a chimeric Washington strain with a South African spike gene (Wash SA-B.1.351), and isogenic recombinant variants with designed mutations or deletions at positions 69-70, 417, 484, 501, and/or 614 of the spike protein. Several highly neutralizing mAbs engaging the receptor binding domain (RBD) or N-terminal domain (NTD) lost inhibitory activity against Wash SA-B.1.351 or recombinant variants with an E484K spike mutation. Most convalescent sera and virtually all mRNA vaccine-induced immune sera tested showed markedly diminished neutralizing activity against the Wash SA-B.1.351 strain or recombinant viruses containing mutations at position 484 and 501. We also noted that cell line selection used for growth of virus stocks or neutralization assays can impact the potency of antibodies against different SARS-CoV-2 variants, which has implications for assay standardization and congruence of results across laboratories. As several antibodies binding specific regions of the RBD and NTD show loss-of-neutralization potency in vitro against emerging variants, updated mAb cocktails, targeting of highly conserved regions, enhancement of mAb potency, or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.
1000 Sacherschließung
lokal Assay Standardization
gnd 1206347392 COVID-19
lokal Antibody-based Countermeasures
lokal Pseudoviruses, Chimeric Washington Strain
lokal South African Spike Gene
lokal Vaccine Efficacy
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/RGlhbW9uZCwgTWljaGFlbA==|https://frl.publisso.de/adhoc/uri/Q2hlbiwgUml0YQ==|https://orcid.org/0000-0003-0918-016X|https://orcid.org/0000-0001-7331-5511|https://frl.publisso.de/adhoc/uri/WmhhbmcsIFhpYW53ZW4=|https://frl.publisso.de/adhoc/uri/VmFuQmxhcmdhbiwgTGF1cmEg|https://frl.publisso.de/adhoc/uri/TGl1LCBZYW5nIA==|https://frl.publisso.de/adhoc/uri/TGl1LCBKaWFueWluZyA=|https://frl.publisso.de/adhoc/uri/RXJyaWNvLCBKb2hu|https://frl.publisso.de/adhoc/uri/V2lua2xlciwgRW1tYSA=|https://frl.publisso.de/adhoc/uri/U3VyeWFkZXZhcmEsIE5hdmVlbmNoYW5kcmEg|https://frl.publisso.de/adhoc/uri/VGFoYW4sIFN0ZXBoZW4g|https://frl.publisso.de/adhoc/uri/VHVybmVyLCBKYWNrc29uIA==|https://orcid.org/0000-0002-9199-1000|https://orcid.org/0000-0002-8077-6751|https://frl.publisso.de/adhoc/uri/VGhhcGEsIE1haGltYSA=|https://frl.publisso.de/adhoc/uri/V2FuZywgRGF2aWQg|https://frl.publisso.de/adhoc/uri/Qm9vbiwgQW5kcmlhbnVzIA==|https://frl.publisso.de/adhoc/uri/UGludG8sIERvcmEg|https://frl.publisso.de/adhoc/uri/UHJlc3RpLCBSYWNoZWwg|https://frl.publisso.de/adhoc/uri/T_KAmUhhbGxvcmFuLCBKYW5lIA==|https://frl.publisso.de/adhoc/uri/S2ltLCBBbGZyZWQg|https://frl.publisso.de/adhoc/uri/RGVlcGFrLCBQYXJha2thbCA=|https://orcid.org/0000-0002-8544-2689|https://orcid.org/0000-0002-5797-1364|https://orcid.org/0000-0001-8580-7628|https://orcid.org/0000-0002-0049-1079|https://frl.publisso.de/adhoc/uri/RHJvaXQsIExpbmRzYXkg|https://orcid.org/0000-0002-6129-2532|https://orcid.org/0000-0001-5553-1616|https://frl.publisso.de/adhoc/uri/R2lsY2h1aywgUGF2bG8g
1000 Label
1000 Förderer
  1. National Institutes of Health |
  2. Defense Advanced Research Projects Agency |
  3. Vanderbilt University |
  4. Merck KGaA |
  5. Helen Hay Whitney Foundation |
  6. Sealy & Smith Foundation |
  7. Alice Kleberg Reynolds Foundation |
  8. John S. Dunn Foundation |
  9. Amon G. Carter Foundation |
  10. Gillson Longenbaugh Foundation |
  11. Summerfield G. Roberts Foundation |
  12. American College of Gastroenterology |
1000 Fördernummer
  1. 75N93019C00062; 75N93019C00051; 75N93019C00074; HHSN272201400006C; HHSN272201400008C; R01 AI157155; U01 AI151810; R01 AI142759; R01 AI134907; R01 AI145617; UL1 TR001439; P30 AR073752; U01AI141990
  2. HR001117S0019
  3. -
  4. -
  5. F30 AI152327; 5T32CA009547
  6. -
  7. -
  8. -
  9. -
  10. -
  11. -
  12. -
1000 Förderprogramm
  1. -
  2. -
  3. Dolly Parton COVID-19 Research Fund
  4. Future Insight Prize
  5. postdoctoral fellowship
  6. -
  7. -
  8. -
  9. -
  10. -
  11. -
  12. Junior Faculty Development Award
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer National Institutes of Health |
    1000 Förderprogramm -
    1000 Fördernummer 75N93019C00062; 75N93019C00051; 75N93019C00074; HHSN272201400006C; HHSN272201400008C; R01 AI157155; U01 AI151810; R01 AI142759; R01 AI134907; R01 AI145617; UL1 TR001439; P30 AR073752; U01AI141990
  2. 1000 joinedFunding-child
    1000 Förderer Defense Advanced Research Projects Agency |
    1000 Förderprogramm -
    1000 Fördernummer HR001117S0019
  3. 1000 joinedFunding-child
    1000 Förderer Vanderbilt University |
    1000 Förderprogramm Dolly Parton COVID-19 Research Fund
    1000 Fördernummer -
  4. 1000 joinedFunding-child
    1000 Förderer Merck KGaA |
    1000 Förderprogramm Future Insight Prize
    1000 Fördernummer -
  5. 1000 joinedFunding-child
    1000 Förderer Helen Hay Whitney Foundation |
    1000 Förderprogramm postdoctoral fellowship
    1000 Fördernummer F30 AI152327; 5T32CA009547
  6. 1000 joinedFunding-child
    1000 Förderer Sealy & Smith Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  7. 1000 joinedFunding-child
    1000 Förderer Alice Kleberg Reynolds Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  8. 1000 joinedFunding-child
    1000 Förderer John S. Dunn Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  9. 1000 joinedFunding-child
    1000 Förderer Amon G. Carter Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  10. 1000 joinedFunding-child
    1000 Förderer Gillson Longenbaugh Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  11. 1000 joinedFunding-child
    1000 Förderer Summerfield G. Roberts Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  12. 1000 joinedFunding-child
    1000 Förderer American College of Gastroenterology |
    1000 Förderprogramm Junior Faculty Development Award
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6428130.rdf
1000 Erstellt am 2021-06-10T10:20:27.715+0200
1000 Erstellt von 284
1000 beschreibt frl:6428130
1000 Bearbeitet von 25
1000 Zuletzt bearbeitet 2022-10-12T10:07:26.152+0200
1000 Objekt bearb. Wed Oct 12 10:07:25 CEST 2022
1000 Vgl. frl:6428130
1000 Oai Id
  1. oai:frl.publisso.de:frl:6428130 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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