SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines

Autores
Bowen, John E.; Park, Young Jun; Stewart, Cameron; Brown, Jack T.; Sharkey, William K.; Walls, Alexandra C.; Joshi, Anshu; Sprouse, Kaitlin R.; McCallum, Matthew; Tortorici, M. Alejandra; Franko, Nicholas M.; Logue, Jennifer K.; Mazzitelli, Ignacio Gabriel; Nguyen, Annalee W.; Silva, Rui P.; Huang, Yimin; Low, Jun Siong; Jerak, Josipa; Tiles, Sasha W.; Ahmed, Kumail; Shariq, Asefa; Dan, Jennifer M.; Zhang, Zeli; Weiskopf, Daniela; Sette, Alessandro; Snell, Gyorgy; Posavad, Christine M.; Iqbal, Najeeha Talat; Geffner, Jorge Raúl; Bandera, Alessandra
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S1 subunit and that variant cross-neutralization is mediated solely by receptor binding domain–specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants than current technologies.
Fil: Bowen, John E.. University of Washington; Estados Unidos
Fil: Park, Young Jun. University of Washington; Estados Unidos
Fil: Stewart, Cameron. University of Washington; Estados Unidos
Fil: Brown, Jack T.. University of Washington; Estados Unidos
Fil: Sharkey, William K.. University of Washington; Estados Unidos
Fil: Walls, Alexandra C.. University of Washington; Estados Unidos
Fil: Joshi, Anshu. University of Washington; Estados Unidos
Fil: Sprouse, Kaitlin R.. University of Washington; Estados Unidos
Fil: McCallum, Matthew. University of Washington; Estados Unidos
Fil: Tortorici, M. Alejandra. University of Washington; Estados Unidos
Fil: Franko, Nicholas M.. University of Washington; Estados Unidos
Fil: Logue, Jennifer K.. University of Washington; Estados Unidos
Fil: Mazzitelli, Ignacio Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Nguyen, Annalee W.. University of Texas at Austin; Estados Unidos
Fil: Silva, Rui P.. University of Texas at Austin; Estados Unidos
Fil: Huang, Yimin. University of Texas at Austin; Estados Unidos
Fil: Low, Jun Siong. Università della Svizzera Italiana; Suiza
Fil: Jerak, Josipa. Università della Svizzera Italiana; Suiza
Fil: Tiles, Sasha W.. University of Washington. School of Medicine; Estados Unidos
Fil: Ahmed, Kumail. The Aga Khan University; Pakistán
Fil: Shariq, Asefa. The Aga Khan University; Pakistán
Fil: Dan, Jennifer M.. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California; Estados Unidos
Fil: Zhang, Zeli. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California; Estados Unidos
Fil: Weiskopf, Daniela. University of California; Estados Unidos. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Sette, Alessandro. University of California; Estados Unidos. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Snell, Gyorgy. Vir Biotechnology; Estados Unidos
Fil: Posavad, Christine M.. Fred Hutchinson Cancer Center; Estados Unidos
Fil: Iqbal, Najeeha Talat. The Aga Khan University; Pakistán
Fil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Bandera, Alessandra. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico; Italia
Materia
SARS-CoV-2
Neutralizing antibodies
COVID-19
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/230606

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccinesBowen, John E.Park, Young JunStewart, CameronBrown, Jack T.Sharkey, William K.Walls, Alexandra C.Joshi, AnshuSprouse, Kaitlin R.McCallum, MatthewTortorici, M. AlejandraFranko, Nicholas M.Logue, Jennifer K.Mazzitelli, Ignacio GabrielNguyen, Annalee W.Silva, Rui P.Huang, YiminLow, Jun SiongJerak, JosipaTiles, Sasha W.Ahmed, KumailShariq, AsefaDan, Jennifer M.Zhang, ZeliWeiskopf, DanielaSette, AlessandroSnell, GyorgyPosavad, Christine M.Iqbal, Najeeha TalatGeffner, Jorge RaúlBandera, AlessandraSARS-CoV-2Neutralizing antibodiesCOVID-19https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S1 subunit and that variant cross-neutralization is mediated solely by receptor binding domain–specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants than current technologies.Fil: Bowen, John E.. University of Washington; Estados UnidosFil: Park, Young Jun. University of Washington; Estados UnidosFil: Stewart, Cameron. University of Washington; Estados UnidosFil: Brown, Jack T.. University of Washington; Estados UnidosFil: Sharkey, William K.. University of Washington; Estados UnidosFil: Walls, Alexandra C.. University of Washington; Estados UnidosFil: Joshi, Anshu. University of Washington; Estados UnidosFil: Sprouse, Kaitlin R.. University of Washington; Estados UnidosFil: McCallum, Matthew. University of Washington; Estados UnidosFil: Tortorici, M. Alejandra. University of Washington; Estados UnidosFil: Franko, Nicholas M.. University of Washington; Estados UnidosFil: Logue, Jennifer K.. University of Washington; Estados UnidosFil: Mazzitelli, Ignacio Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Nguyen, Annalee W.. University of Texas at Austin; Estados UnidosFil: Silva, Rui P.. University of Texas at Austin; Estados UnidosFil: Huang, Yimin. University of Texas at Austin; Estados UnidosFil: Low, Jun Siong. Università della Svizzera Italiana; SuizaFil: Jerak, Josipa. Università della Svizzera Italiana; SuizaFil: Tiles, Sasha W.. University of Washington. School of Medicine; Estados UnidosFil: Ahmed, Kumail. The Aga Khan University; PakistánFil: Shariq, Asefa. The Aga Khan University; PakistánFil: Dan, Jennifer M.. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California; Estados UnidosFil: Zhang, Zeli. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California; Estados UnidosFil: Weiskopf, Daniela. University of California; Estados Unidos. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Sette, Alessandro. University of California; Estados Unidos. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Snell, Gyorgy. Vir Biotechnology; Estados UnidosFil: Posavad, Christine M.. Fred Hutchinson Cancer Center; Estados UnidosFil: Iqbal, Najeeha Talat. The Aga Khan University; PakistánFil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Bandera, Alessandra. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico; ItaliaAmerican Association for the Advancement of Science2022-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/230606Bowen, John E.; Park, Young Jun; Stewart, Cameron; Brown, Jack T.; Sharkey, William K.; et al.; SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines; American Association for the Advancement of Science; Science Immunology; 7; 78; 12-2022; 1-142470-9468CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1126/SCIIMMUNOL.ADF1421info:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/sciimmunol.adf1421info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:32Zoai:ri.conicet.gov.ar:11336/230606instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:07:32.641CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines
title SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines
spellingShingle SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines
Bowen, John E.
SARS-CoV-2
Neutralizing antibodies
COVID-19
title_short SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines
title_full SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines
title_fullStr SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines
title_full_unstemmed SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines
title_sort SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines
dc.creator.none.fl_str_mv Bowen, John E.
Park, Young Jun
Stewart, Cameron
Brown, Jack T.
Sharkey, William K.
Walls, Alexandra C.
Joshi, Anshu
Sprouse, Kaitlin R.
McCallum, Matthew
Tortorici, M. Alejandra
Franko, Nicholas M.
Logue, Jennifer K.
Mazzitelli, Ignacio Gabriel
Nguyen, Annalee W.
Silva, Rui P.
Huang, Yimin
Low, Jun Siong
Jerak, Josipa
Tiles, Sasha W.
Ahmed, Kumail
Shariq, Asefa
Dan, Jennifer M.
Zhang, Zeli
Weiskopf, Daniela
Sette, Alessandro
Snell, Gyorgy
Posavad, Christine M.
Iqbal, Najeeha Talat
Geffner, Jorge Raúl
Bandera, Alessandra
author Bowen, John E.
author_facet Bowen, John E.
Park, Young Jun
Stewart, Cameron
Brown, Jack T.
Sharkey, William K.
Walls, Alexandra C.
Joshi, Anshu
Sprouse, Kaitlin R.
McCallum, Matthew
Tortorici, M. Alejandra
Franko, Nicholas M.
Logue, Jennifer K.
Mazzitelli, Ignacio Gabriel
Nguyen, Annalee W.
Silva, Rui P.
Huang, Yimin
Low, Jun Siong
Jerak, Josipa
Tiles, Sasha W.
Ahmed, Kumail
Shariq, Asefa
Dan, Jennifer M.
Zhang, Zeli
Weiskopf, Daniela
Sette, Alessandro
Snell, Gyorgy
Posavad, Christine M.
Iqbal, Najeeha Talat
Geffner, Jorge Raúl
Bandera, Alessandra
author_role author
author2 Park, Young Jun
Stewart, Cameron
Brown, Jack T.
Sharkey, William K.
Walls, Alexandra C.
Joshi, Anshu
Sprouse, Kaitlin R.
McCallum, Matthew
Tortorici, M. Alejandra
Franko, Nicholas M.
Logue, Jennifer K.
Mazzitelli, Ignacio Gabriel
Nguyen, Annalee W.
Silva, Rui P.
Huang, Yimin
Low, Jun Siong
Jerak, Josipa
Tiles, Sasha W.
Ahmed, Kumail
Shariq, Asefa
Dan, Jennifer M.
Zhang, Zeli
Weiskopf, Daniela
Sette, Alessandro
Snell, Gyorgy
Posavad, Christine M.
Iqbal, Najeeha Talat
Geffner, Jorge Raúl
Bandera, Alessandra
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SARS-CoV-2
Neutralizing antibodies
COVID-19
topic SARS-CoV-2
Neutralizing antibodies
COVID-19
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S1 subunit and that variant cross-neutralization is mediated solely by receptor binding domain–specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants than current technologies.
Fil: Bowen, John E.. University of Washington; Estados Unidos
Fil: Park, Young Jun. University of Washington; Estados Unidos
Fil: Stewart, Cameron. University of Washington; Estados Unidos
Fil: Brown, Jack T.. University of Washington; Estados Unidos
Fil: Sharkey, William K.. University of Washington; Estados Unidos
Fil: Walls, Alexandra C.. University of Washington; Estados Unidos
Fil: Joshi, Anshu. University of Washington; Estados Unidos
Fil: Sprouse, Kaitlin R.. University of Washington; Estados Unidos
Fil: McCallum, Matthew. University of Washington; Estados Unidos
Fil: Tortorici, M. Alejandra. University of Washington; Estados Unidos
Fil: Franko, Nicholas M.. University of Washington; Estados Unidos
Fil: Logue, Jennifer K.. University of Washington; Estados Unidos
Fil: Mazzitelli, Ignacio Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Nguyen, Annalee W.. University of Texas at Austin; Estados Unidos
Fil: Silva, Rui P.. University of Texas at Austin; Estados Unidos
Fil: Huang, Yimin. University of Texas at Austin; Estados Unidos
Fil: Low, Jun Siong. Università della Svizzera Italiana; Suiza
Fil: Jerak, Josipa. Università della Svizzera Italiana; Suiza
Fil: Tiles, Sasha W.. University of Washington. School of Medicine; Estados Unidos
Fil: Ahmed, Kumail. The Aga Khan University; Pakistán
Fil: Shariq, Asefa. The Aga Khan University; Pakistán
Fil: Dan, Jennifer M.. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California; Estados Unidos
Fil: Zhang, Zeli. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California; Estados Unidos
Fil: Weiskopf, Daniela. University of California; Estados Unidos. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Sette, Alessandro. University of California; Estados Unidos. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Snell, Gyorgy. Vir Biotechnology; Estados Unidos
Fil: Posavad, Christine M.. Fred Hutchinson Cancer Center; Estados Unidos
Fil: Iqbal, Najeeha Talat. The Aga Khan University; Pakistán
Fil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Bandera, Alessandra. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico; Italia
description Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S1 subunit and that variant cross-neutralization is mediated solely by receptor binding domain–specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants than current technologies.
publishDate 2022
dc.date.none.fl_str_mv 2022-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/230606
Bowen, John E.; Park, Young Jun; Stewart, Cameron; Brown, Jack T.; Sharkey, William K.; et al.; SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines; American Association for the Advancement of Science; Science Immunology; 7; 78; 12-2022; 1-14
2470-9468
CONICET Digital
CONICET
url http://hdl.handle.net/11336/230606
identifier_str_mv Bowen, John E.; Park, Young Jun; Stewart, Cameron; Brown, Jack T.; Sharkey, William K.; et al.; SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines; American Association for the Advancement of Science; Science Immunology; 7; 78; 12-2022; 1-14
2470-9468
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1126/SCIIMMUNOL.ADF1421
info:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/sciimmunol.adf1421
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science
publisher.none.fl_str_mv American Association for the Advancement of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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