Antibodies to neutralising epitopes synergistically block the interaction of the receptor‐binding domain of SARS‐CoV‐2 to ACE 2

  1. Pandey, Manisha ORCID logo
  2. Ozberk, Victoria
  3. Eskandari, Sharareh
  4. Shalash, Ahmed ORCID logo
  5. Joyce, Michael A
  6. Saffran, Holly A
  7. Day, Christopher J
  8. Lepletier , Ailin ORCID logo
  9. Spillings, Belinda L
  10. Mills, Jamie-Lee
  11. Calcutt, Ainslie
  12. Fan, Fan
  13. Williams, James T
  14. Stanisic, Danielle I
  15. Hattingh, Laetitia
  16. Gerrard, John
  17. Skwarczynski, Mariusz ORCID logo
  18. Mak, Johnson
  19. Jennings, Michael P
  20. Toth, Istvan ORCID logo
  21. Tyrrell, D Lorne
  22. Good, Michael F

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WeightNameValue
1000 Titel
  • Antibodies to neutralising epitopes synergistically block the interaction of the receptor‐binding domain of SARS‐CoV‐2 to ACE 2
1000 Autor/in
  1. Pandey, Manisha |
  2. Ozberk, Victoria |
  3. Eskandari, Sharareh |
  4. Shalash, Ahmed |
  5. Joyce, Michael A |
  6. Saffran, Holly A |
  7. Day, Christopher J |
  8. Lepletier , Ailin |
  9. Spillings, Belinda L |
  10. Mills, Jamie-Lee |
  11. Calcutt, Ainslie |
  12. Fan, Fan |
  13. Williams, James T |
  14. Stanisic, Danielle I |
  15. Hattingh, Laetitia |
  16. Gerrard, John |
  17. Skwarczynski, Mariusz |
  18. Mak, Johnson |
  19. Jennings, Michael P |
  20. Toth, Istvan |
  21. Tyrrell, D Lorne |
  22. Good, Michael F |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-03-07
1000 Erschienen in
1000 Quellenangabe
  • 10(3):e1260
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1002/cti2.1260 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937407/ |
1000 Ergänzendes Material
  • https://onlinelibrary.wiley.com/doi/10.1002/cti2.1260#support-information-section |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • OBJECTIVES: A major COVID‐19 vaccine strategy is to induce antibodies that prevent interaction between the Spike protein's receptor‐binding domain (RBD) and angiotensin‐converting enzyme 2 (ACE2). These vaccines will also induce T‐cell responses. However, concerns were raised that aberrant vaccine‐induced immune responses may exacerbate disease. We aimed to identify minimal epitopes on the RBD that would induce antibody responses that block the interaction of the RBD and ACE2 as a strategy leading to an effective vaccine with reduced risk of inducing immunopathology. METHODS: We procured a series of overlapping 20‐amino acid peptides spanning the RBD and asked which were recognised by plasma from COVID‐19 convalescent patients. Identified epitopes were conjugated to diphtheria‐toxoid and used to vaccinate mice. Immune sera were tested for binding to the RBD and for their ability to block the interaction of the RBD and ACE2. RESULTS: Seven putative vaccine epitopes were identified. Memory B‐cells (MBCs) specific for one of the epitopes were identified in the blood of convalescent patients. When used to vaccinate mice, six induced antibodies that bound recRBD and three induced antibodies that could partially block the interaction of the RBD and ACE2. However, when the sera were combined in pairs, we observed significantly enhanced inhibition of binding of RBD to ACE2. Two of the peptides were located in the main regions of the RBD known to contact ACE2. Of significant importance to vaccine development, two of the peptides were in regions that are invariant in the UK and South African strains. CONCLUSION: COVID‐19 convalescent patients have SARS‐CoV‐2‐specific antibodies and MBCs, the specificities of which can be defined with short peptides. Epitope‐specific antibodies synergistically block RBD–ACE2 interaction.
1000 Sacherschließung
lokal peptide epitopes
gnd 1206347392 COVID-19
lokal memory B cells
lokal tetramer staining
lokal ACE-2
lokal SARS-CoV-2
lokal receptor-binding domain
lokal vaccine
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-4151-699X|https://frl.publisso.de/adhoc/uri/T3piZXJrLCBWaWN0b3JpYQ==|https://frl.publisso.de/adhoc/uri/RXNrYW5kYXJpLCBTaGFyYXJlaA==|https://orcid.org/0000-0003-3819-4798|https://frl.publisso.de/adhoc/uri/Sm95Y2UsIE1pY2hhZWwgQQ==|https://frl.publisso.de/adhoc/uri/U2FmZnJhbiwgSG9sbHkgQQ==|https://frl.publisso.de/adhoc/uri/RGF5LCBDaHJpc3RvcGhlciBK|https://orcid.org/0000-0002-1371-7313|https://frl.publisso.de/adhoc/uri/U3BpbGxpbmdzLCBCZWxpbmRhIEw=|https://frl.publisso.de/adhoc/uri/TWlsbHMsIEphbWllLUxlZQ==|https://frl.publisso.de/adhoc/uri/Q2FsY3V0dCwgQWluc2xpZQ==|https://frl.publisso.de/adhoc/uri/RmFuLCBGYW4=|https://frl.publisso.de/adhoc/uri/V2lsbGlhbXMsIEphbWVzIFQ=|https://frl.publisso.de/adhoc/uri/U3RhbmlzaWMsIERhbmllbGxlIEk=|https://frl.publisso.de/adhoc/uri/SGF0dGluZ2gsIExhZXRpdGlh|https://frl.publisso.de/adhoc/uri/R2VycmFyZCwgSm9obg==|https://orcid.org/0000-0001-7257-807X|https://frl.publisso.de/adhoc/uri/TWFrLCBKb2huc29u|https://frl.publisso.de/adhoc/uri/SmVubmluZ3MsIE1pY2hhZWwgUA==|https://orcid.org/0000-0002-4572-397X|https://frl.publisso.de/adhoc/uri/VHlycmVsbCwgRCBMb3JuZQ==|https://frl.publisso.de/adhoc/uri/R29vZCwgTWljaGFlbCBG
1000 Label
1000 Förderer
  1. National Health and Medical Research Council |
1000 Fördernummer
  1. 1138466; 1132975; 1174091
1000 Förderprogramm
  1. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer National Health and Medical Research Council |
    1000 Förderprogramm -
    1000 Fördernummer 1138466; 1132975; 1174091
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6426996.rdf
1000 Erstellt am 2021-04-21T13:27:02.673+0200
1000 Erstellt von 218
1000 beschreibt frl:6426996
1000 Bearbeitet von 25
1000 Zuletzt bearbeitet 2021-05-31T09:50:41.695+0200
1000 Objekt bearb. Mon May 31 09:50:27 CEST 2021
1000 Vgl. frl:6426996
1000 Oai Id
  1. oai:frl.publisso.de:frl:6426996 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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