Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses

More than 80% of SARS-CoV-2 variants, including Alpha and Omicron, contain an N501Y mutation in the receptor-binding domain (RBD) of the spike protein. The N501Y change is an adaptive mutation enabling tighter interaction with the human ACE2 receptor. We have developed a broadly neutralizing antibod...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Bo-Seong Jeong [verfasserIn] Joon Young Jeon [verfasserIn] Chih-Jen Lai [verfasserIn] Hye-Yeoung Yun [verfasserIn] Jae U. Jung [verfasserIn] Byung-Ha Oh [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	SARS-CoV-2 viral evolution key epitope computational affinity maturation broadly neutralizing antibody broad-spectrum vaccine

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 13(2022)
Übergeordnetes Werk:	volume:13 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2022.1049867

Katalog-ID:	DOAJ010032622

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allfields	10.3389/fimmu.2022.1049867 doi (DE-627)DOAJ010032622 (DE-599)DOAJbfc3c6c3b8b14652a2710c45c89cdd42 DE-627 ger DE-627 rakwb eng RC581-607 Bo-Seong Jeong verfasserin aut Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier More than 80% of SARS-CoV-2 variants, including Alpha and Omicron, contain an N501Y mutation in the receptor-binding domain (RBD) of the spike protein. The N501Y change is an adaptive mutation enabling tighter interaction with the human ACE2 receptor. We have developed a broadly neutralizing antibody (nAb), D27LEY, whose binding affinity was intentionally optimized for Y501. This N501Y-centric antibody not only interacts with the Y501-containing RBDs of SARS-CoV-2 variants, including Omicron, with pico- or subnanomolar binding affinity, but also binds tightly to the RBDs with a different amino acid at residue 501. The crystal structure of the Fab fragment of D27LEY bound to the RBD of the Alpha variant reveals that the Y501-containing loop adopts a ribbon-like topology and serves as a small but major epitope in which Y501 is a part of extensive intermolecular interactions. A hydrophobic cleft on the most conserved surface of the RBD core serves as another major binding epitope. These data explain the broad and potent cross-reactivity of this N501Y-centric antibody, and suggest that a vaccine antigenic component composed of the RBD core and a part of receptor-binding motif (RBM) containing tyrosine at residue 501 might elicit broad and potent humoral responses across sarbecoviruses. SARS-CoV-2 viral evolution key epitope computational affinity maturation broadly neutralizing antibody broad-spectrum vaccine Immunologic diseases. Allergy Joon Young Jeon verfasserin aut Chih-Jen Lai verfasserin aut Hye-Yeoung Yun verfasserin aut Jae U. Jung verfasserin aut Byung-Ha Oh verfasserin aut Byung-Ha Oh verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1049867 kostenfrei https://doaj.org/article/bfc3c6c3b8b14652a2710c45c89cdd42 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1049867/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
spelling	10.3389/fimmu.2022.1049867 doi (DE-627)DOAJ010032622 (DE-599)DOAJbfc3c6c3b8b14652a2710c45c89cdd42 DE-627 ger DE-627 rakwb eng RC581-607 Bo-Seong Jeong verfasserin aut Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier More than 80% of SARS-CoV-2 variants, including Alpha and Omicron, contain an N501Y mutation in the receptor-binding domain (RBD) of the spike protein. The N501Y change is an adaptive mutation enabling tighter interaction with the human ACE2 receptor. We have developed a broadly neutralizing antibody (nAb), D27LEY, whose binding affinity was intentionally optimized for Y501. This N501Y-centric antibody not only interacts with the Y501-containing RBDs of SARS-CoV-2 variants, including Omicron, with pico- or subnanomolar binding affinity, but also binds tightly to the RBDs with a different amino acid at residue 501. The crystal structure of the Fab fragment of D27LEY bound to the RBD of the Alpha variant reveals that the Y501-containing loop adopts a ribbon-like topology and serves as a small but major epitope in which Y501 is a part of extensive intermolecular interactions. A hydrophobic cleft on the most conserved surface of the RBD core serves as another major binding epitope. These data explain the broad and potent cross-reactivity of this N501Y-centric antibody, and suggest that a vaccine antigenic component composed of the RBD core and a part of receptor-binding motif (RBM) containing tyrosine at residue 501 might elicit broad and potent humoral responses across sarbecoviruses. SARS-CoV-2 viral evolution key epitope computational affinity maturation broadly neutralizing antibody broad-spectrum vaccine Immunologic diseases. Allergy Joon Young Jeon verfasserin aut Chih-Jen Lai verfasserin aut Hye-Yeoung Yun verfasserin aut Jae U. Jung verfasserin aut Byung-Ha Oh verfasserin aut Byung-Ha Oh verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1049867 kostenfrei https://doaj.org/article/bfc3c6c3b8b14652a2710c45c89cdd42 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1049867/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfields_unstemmed	10.3389/fimmu.2022.1049867 doi (DE-627)DOAJ010032622 (DE-599)DOAJbfc3c6c3b8b14652a2710c45c89cdd42 DE-627 ger DE-627 rakwb eng RC581-607 Bo-Seong Jeong verfasserin aut Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier More than 80% of SARS-CoV-2 variants, including Alpha and Omicron, contain an N501Y mutation in the receptor-binding domain (RBD) of the spike protein. The N501Y change is an adaptive mutation enabling tighter interaction with the human ACE2 receptor. We have developed a broadly neutralizing antibody (nAb), D27LEY, whose binding affinity was intentionally optimized for Y501. This N501Y-centric antibody not only interacts with the Y501-containing RBDs of SARS-CoV-2 variants, including Omicron, with pico- or subnanomolar binding affinity, but also binds tightly to the RBDs with a different amino acid at residue 501. The crystal structure of the Fab fragment of D27LEY bound to the RBD of the Alpha variant reveals that the Y501-containing loop adopts a ribbon-like topology and serves as a small but major epitope in which Y501 is a part of extensive intermolecular interactions. A hydrophobic cleft on the most conserved surface of the RBD core serves as another major binding epitope. These data explain the broad and potent cross-reactivity of this N501Y-centric antibody, and suggest that a vaccine antigenic component composed of the RBD core and a part of receptor-binding motif (RBM) containing tyrosine at residue 501 might elicit broad and potent humoral responses across sarbecoviruses. SARS-CoV-2 viral evolution key epitope computational affinity maturation broadly neutralizing antibody broad-spectrum vaccine Immunologic diseases. Allergy Joon Young Jeon verfasserin aut Chih-Jen Lai verfasserin aut Hye-Yeoung Yun verfasserin aut Jae U. Jung verfasserin aut Byung-Ha Oh verfasserin aut Byung-Ha Oh verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1049867 kostenfrei https://doaj.org/article/bfc3c6c3b8b14652a2710c45c89cdd42 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1049867/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfieldsGer	10.3389/fimmu.2022.1049867 doi (DE-627)DOAJ010032622 (DE-599)DOAJbfc3c6c3b8b14652a2710c45c89cdd42 DE-627 ger DE-627 rakwb eng RC581-607 Bo-Seong Jeong verfasserin aut Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier More than 80% of SARS-CoV-2 variants, including Alpha and Omicron, contain an N501Y mutation in the receptor-binding domain (RBD) of the spike protein. The N501Y change is an adaptive mutation enabling tighter interaction with the human ACE2 receptor. We have developed a broadly neutralizing antibody (nAb), D27LEY, whose binding affinity was intentionally optimized for Y501. This N501Y-centric antibody not only interacts with the Y501-containing RBDs of SARS-CoV-2 variants, including Omicron, with pico- or subnanomolar binding affinity, but also binds tightly to the RBDs with a different amino acid at residue 501. The crystal structure of the Fab fragment of D27LEY bound to the RBD of the Alpha variant reveals that the Y501-containing loop adopts a ribbon-like topology and serves as a small but major epitope in which Y501 is a part of extensive intermolecular interactions. A hydrophobic cleft on the most conserved surface of the RBD core serves as another major binding epitope. These data explain the broad and potent cross-reactivity of this N501Y-centric antibody, and suggest that a vaccine antigenic component composed of the RBD core and a part of receptor-binding motif (RBM) containing tyrosine at residue 501 might elicit broad and potent humoral responses across sarbecoviruses. SARS-CoV-2 viral evolution key epitope computational affinity maturation broadly neutralizing antibody broad-spectrum vaccine Immunologic diseases. Allergy Joon Young Jeon verfasserin aut Chih-Jen Lai verfasserin aut Hye-Yeoung Yun verfasserin aut Jae U. Jung verfasserin aut Byung-Ha Oh verfasserin aut Byung-Ha Oh verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1049867 kostenfrei https://doaj.org/article/bfc3c6c3b8b14652a2710c45c89cdd42 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1049867/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfieldsSound	10.3389/fimmu.2022.1049867 doi (DE-627)DOAJ010032622 (DE-599)DOAJbfc3c6c3b8b14652a2710c45c89cdd42 DE-627 ger DE-627 rakwb eng RC581-607 Bo-Seong Jeong verfasserin aut Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier More than 80% of SARS-CoV-2 variants, including Alpha and Omicron, contain an N501Y mutation in the receptor-binding domain (RBD) of the spike protein. The N501Y change is an adaptive mutation enabling tighter interaction with the human ACE2 receptor. We have developed a broadly neutralizing antibody (nAb), D27LEY, whose binding affinity was intentionally optimized for Y501. This N501Y-centric antibody not only interacts with the Y501-containing RBDs of SARS-CoV-2 variants, including Omicron, with pico- or subnanomolar binding affinity, but also binds tightly to the RBDs with a different amino acid at residue 501. The crystal structure of the Fab fragment of D27LEY bound to the RBD of the Alpha variant reveals that the Y501-containing loop adopts a ribbon-like topology and serves as a small but major epitope in which Y501 is a part of extensive intermolecular interactions. A hydrophobic cleft on the most conserved surface of the RBD core serves as another major binding epitope. These data explain the broad and potent cross-reactivity of this N501Y-centric antibody, and suggest that a vaccine antigenic component composed of the RBD core and a part of receptor-binding motif (RBM) containing tyrosine at residue 501 might elicit broad and potent humoral responses across sarbecoviruses. SARS-CoV-2 viral evolution key epitope computational affinity maturation broadly neutralizing antibody broad-spectrum vaccine Immunologic diseases. Allergy Joon Young Jeon verfasserin aut Chih-Jen Lai verfasserin aut Hye-Yeoung Yun verfasserin aut Jae U. Jung verfasserin aut Byung-Ha Oh verfasserin aut Byung-Ha Oh verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1049867 kostenfrei https://doaj.org/article/bfc3c6c3b8b14652a2710c45c89cdd42 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1049867/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
language	English
source	In Frontiers in Immunology 13(2022) volume:13 year:2022
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topic_facet	SARS-CoV-2 viral evolution key epitope computational affinity maturation broadly neutralizing antibody broad-spectrum vaccine Immunologic diseases. Allergy
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container_title	Frontiers in Immunology
authorswithroles_txt_mv	Bo-Seong Jeong @@aut@@ Joon Young Jeon @@aut@@ Chih-Jen Lai @@aut@@ Hye-Yeoung Yun @@aut@@ Jae U. Jung @@aut@@ Byung-Ha Oh @@aut@@
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callnumber-first	R - Medicine
author	Bo-Seong Jeong
spellingShingle	Bo-Seong Jeong misc RC581-607 misc SARS-CoV-2 misc viral evolution misc key epitope misc computational affinity maturation misc broadly neutralizing antibody misc broad-spectrum vaccine misc Immunologic diseases. Allergy Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses
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topic_title	RC581-607 Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses SARS-CoV-2 viral evolution key epitope computational affinity maturation broadly neutralizing antibody broad-spectrum vaccine
topic	misc RC581-607 misc SARS-CoV-2 misc viral evolution misc key epitope misc computational affinity maturation misc broadly neutralizing antibody misc broad-spectrum vaccine misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc SARS-CoV-2 misc viral evolution misc key epitope misc computational affinity maturation misc broadly neutralizing antibody misc broad-spectrum vaccine misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc SARS-CoV-2 misc viral evolution misc key epitope misc computational affinity maturation misc broadly neutralizing antibody misc broad-spectrum vaccine misc Immunologic diseases. Allergy
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title	Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses
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title_full	Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses
author_sort	Bo-Seong Jeong
journal	Frontiers in Immunology
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author_browse	Bo-Seong Jeong Joon Young Jeon Chih-Jen Lai Hye-Yeoung Yun Jae U. Jung Byung-Ha Oh
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title_sort	structural basis for the broad and potent cross-reactivity of an n501y-centric antibody against sarbecoviruses
callnumber	RC581-607
title_auth	Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses
abstract	More than 80% of SARS-CoV-2 variants, including Alpha and Omicron, contain an N501Y mutation in the receptor-binding domain (RBD) of the spike protein. The N501Y change is an adaptive mutation enabling tighter interaction with the human ACE2 receptor. We have developed a broadly neutralizing antibody (nAb), D27LEY, whose binding affinity was intentionally optimized for Y501. This N501Y-centric antibody not only interacts with the Y501-containing RBDs of SARS-CoV-2 variants, including Omicron, with pico- or subnanomolar binding affinity, but also binds tightly to the RBDs with a different amino acid at residue 501. The crystal structure of the Fab fragment of D27LEY bound to the RBD of the Alpha variant reveals that the Y501-containing loop adopts a ribbon-like topology and serves as a small but major epitope in which Y501 is a part of extensive intermolecular interactions. A hydrophobic cleft on the most conserved surface of the RBD core serves as another major binding epitope. These data explain the broad and potent cross-reactivity of this N501Y-centric antibody, and suggest that a vaccine antigenic component composed of the RBD core and a part of receptor-binding motif (RBM) containing tyrosine at residue 501 might elicit broad and potent humoral responses across sarbecoviruses.
abstractGer	More than 80% of SARS-CoV-2 variants, including Alpha and Omicron, contain an N501Y mutation in the receptor-binding domain (RBD) of the spike protein. The N501Y change is an adaptive mutation enabling tighter interaction with the human ACE2 receptor. We have developed a broadly neutralizing antibody (nAb), D27LEY, whose binding affinity was intentionally optimized for Y501. This N501Y-centric antibody not only interacts with the Y501-containing RBDs of SARS-CoV-2 variants, including Omicron, with pico- or subnanomolar binding affinity, but also binds tightly to the RBDs with a different amino acid at residue 501. The crystal structure of the Fab fragment of D27LEY bound to the RBD of the Alpha variant reveals that the Y501-containing loop adopts a ribbon-like topology and serves as a small but major epitope in which Y501 is a part of extensive intermolecular interactions. A hydrophobic cleft on the most conserved surface of the RBD core serves as another major binding epitope. These data explain the broad and potent cross-reactivity of this N501Y-centric antibody, and suggest that a vaccine antigenic component composed of the RBD core and a part of receptor-binding motif (RBM) containing tyrosine at residue 501 might elicit broad and potent humoral responses across sarbecoviruses.
abstract_unstemmed	More than 80% of SARS-CoV-2 variants, including Alpha and Omicron, contain an N501Y mutation in the receptor-binding domain (RBD) of the spike protein. The N501Y change is an adaptive mutation enabling tighter interaction with the human ACE2 receptor. We have developed a broadly neutralizing antibody (nAb), D27LEY, whose binding affinity was intentionally optimized for Y501. This N501Y-centric antibody not only interacts with the Y501-containing RBDs of SARS-CoV-2 variants, including Omicron, with pico- or subnanomolar binding affinity, but also binds tightly to the RBDs with a different amino acid at residue 501. The crystal structure of the Fab fragment of D27LEY bound to the RBD of the Alpha variant reveals that the Y501-containing loop adopts a ribbon-like topology and serves as a small but major epitope in which Y501 is a part of extensive intermolecular interactions. A hydrophobic cleft on the most conserved surface of the RBD core serves as another major binding epitope. These data explain the broad and potent cross-reactivity of this N501Y-centric antibody, and suggest that a vaccine antigenic component composed of the RBD core and a part of receptor-binding motif (RBM) containing tyrosine at residue 501 might elicit broad and potent humoral responses across sarbecoviruses.
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700
title_short	Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses
url	https://doi.org/10.3389/fimmu.2022.1049867 https://doaj.org/article/bfc3c6c3b8b14652a2710c45c89cdd42 https://www.frontiersin.org/articles/10.3389/fimmu.2022.1049867/full https://doaj.org/toc/1664-3224
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author2	Joon Young Jeon Chih-Jen Lai Hye-Yeoung Yun Jae U. Jung Byung-Ha Oh
author2Str	Joon Young Jeon Chih-Jen Lai Hye-Yeoung Yun Jae U. Jung Byung-Ha Oh
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up_date	2024-07-04T01:59:04.549Z
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These data explain the broad and potent cross-reactivity of this N501Y-centric antibody, and suggest that a vaccine antigenic component composed of the RBD core and a part of receptor-binding motif (RBM) containing tyrosine at residue 501 might elicit broad and potent humoral responses across sarbecoviruses.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">SARS-CoV-2</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">viral evolution</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">key epitope</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">computational affinity maturation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">broadly neutralizing antibody</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">broad-spectrum vaccine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Immunologic diseases. 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Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses

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