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
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 Técnicas2025-09-29T10:33:45Zoai: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:34982025-09-29 10:33:45.444CONICET 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
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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
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repository.mail.fl_str_mv	dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines

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