Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses

Autores
Sui, Jianhua; Hwang, William C.; Perez, Sandra; Wei, Ge; Aird, Daniel; Chen, Li-Mei; Santelli, Eugenio; Stec, Boguslaw; Cadwell, Greg; Ali, Maryam; Wan, Hongquan; Murakami, Akikazu; Yammanuru, Anuradha; Han, Thomas; Cox, Nancy J.; Bankston, Laurie A.; Donis, Ruben O.; Liddington, Robert C.; Marasco, Wayne A.
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.
Fil: Sui, Jianhua. Harvard Medical School; Estados Unidos. Dana-farber Cancer Institute; Estados Unidos
Fil: Hwang, William C.. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Perez, Sandra. National Center For Immunization And Respiratory Diseases; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wei, Ge. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Aird, Daniel. Harvard Medical School; Estados Unidos. Dana-farber Cancer Institute; Estados Unidos
Fil: Chen, Li-Mei. National Center For Immunization And Respiratory Diseases; Estados Unidos
Fil: Santelli, Eugenio. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Stec, Boguslaw. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Cadwell, Greg. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Ali, Maryam. Dana-farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Wan, Hongquan. National Center For Immunization And Respiratory Diseases; Estados Unidos
Fil: Murakami, Akikazu. Harvard Medical School; Estados Unidos. Dana-farber Cancer Institute; Estados Unidos
Fil: Yammanuru, Anuradha. Dana-farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Han, Thomas. Harvard Medical School; Estados Unidos. Dana-farber Cancer Institute; Estados Unidos
Fil: Cox, Nancy J.. National Center For Immunization And Respiratory Diseases; Estados Unidos
Fil: Bankston, Laurie A.. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Donis, Ruben O.. National Center For Immunization And Respiratory Diseases; Estados Unidos
Fil: Liddington, Robert C.. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Marasco, Wayne A.. Dana-farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados Unidos
Materia
INFLUENZA
MONOCLONAL ANTIBODIES
IMMUNOTHERAPY
H5N1
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/96252
Acceder
id CONICETDig_6cc08c9662742f539e9088f396438359
oai_identifier_str oai:ri.conicet.gov.ar:11336/96252
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Structural and functional bases for broad-spectrum neutralization of avian and human influenza A virusesSui, JianhuaHwang, William C.Perez, SandraWei, GeAird, DanielChen, Li-MeiSantelli, EugenioStec, BoguslawCadwell, GregAli, MaryamWan, HongquanMurakami, AkikazuYammanuru, AnuradhaHan, ThomasCox, Nancy J.Bankston, Laurie A.Donis, Ruben O.Liddington, Robert C.Marasco, Wayne A.INFLUENZAMONOCLONAL ANTIBODIESIMMUNOTHERAPYH5N1https://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.Fil: Sui, Jianhua. Harvard Medical School; Estados Unidos. Dana-farber Cancer Institute; Estados UnidosFil: Hwang, William C.. Sanford Burnham Prebys Medical Discovery Institute; Estados UnidosFil: Perez, Sandra. National Center For Immunization And Respiratory Diseases; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wei, Ge. Sanford Burnham Prebys Medical Discovery Institute; Estados UnidosFil: Aird, Daniel. Harvard Medical School; Estados Unidos. Dana-farber Cancer Institute; Estados UnidosFil: Chen, Li-Mei. National Center For Immunization And Respiratory Diseases; Estados UnidosFil: Santelli, Eugenio. Sanford Burnham Prebys Medical Discovery Institute; Estados UnidosFil: Stec, Boguslaw. Sanford Burnham Prebys Medical Discovery Institute; Estados UnidosFil: Cadwell, Greg. Sanford Burnham Prebys Medical Discovery Institute; Estados UnidosFil: Ali, Maryam. Dana-farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados UnidosFil: Wan, Hongquan. National Center For Immunization And Respiratory Diseases; Estados UnidosFil: Murakami, Akikazu. Harvard Medical School; Estados Unidos. Dana-farber Cancer Institute; Estados UnidosFil: Yammanuru, Anuradha. Dana-farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados UnidosFil: Han, Thomas. Harvard Medical School; Estados Unidos. Dana-farber Cancer Institute; Estados UnidosFil: Cox, Nancy J.. National Center For Immunization And Respiratory Diseases; Estados UnidosFil: Bankston, Laurie A.. Sanford Burnham Prebys Medical Discovery Institute; Estados UnidosFil: Donis, Ruben O.. National Center For Immunization And Respiratory Diseases; Estados UnidosFil: Liddington, Robert C.. Sanford Burnham Prebys Medical Discovery Institute; Estados UnidosFil: Marasco, Wayne A.. Dana-farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados UnidosNature Publishing Group2009-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96252Sui, Jianhua; Hwang, William C.; Perez, Sandra; Wei, Ge; Aird, Daniel; et al.; Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses; Nature Publishing Group; Nature Structural and Molecular Biology; 16; 3; 3-2009; 265-2731072-83681545-9985CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/nsmb.1566info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nsmb.1566info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692245/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:41:40Zoai:ri.conicet.gov.ar:11336/96252instacron: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:34982025-09-17 10:41:40.744CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses
title Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses
spellingShingle Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses
Sui, Jianhua
INFLUENZA
MONOCLONAL ANTIBODIES
IMMUNOTHERAPY
H5N1
title_short Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses
title_full Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses
title_fullStr Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses
title_full_unstemmed Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses
title_sort Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses
dc.creator.none.fl_str_mv Sui, Jianhua
Hwang, William C.
Perez, Sandra
Wei, Ge
Aird, Daniel
Chen, Li-Mei
Santelli, Eugenio
Stec, Boguslaw
Cadwell, Greg
Ali, Maryam
Wan, Hongquan
Murakami, Akikazu
Yammanuru, Anuradha
Han, Thomas
Cox, Nancy J.
Bankston, Laurie A.
Donis, Ruben O.
Liddington, Robert C.
Marasco, Wayne A.
author Sui, Jianhua
author_facet Sui, Jianhua
Hwang, William C.
Perez, Sandra
Wei, Ge
Aird, Daniel
Chen, Li-Mei
Santelli, Eugenio
Stec, Boguslaw
Cadwell, Greg
Ali, Maryam
Wan, Hongquan
Murakami, Akikazu
Yammanuru, Anuradha
Han, Thomas
Cox, Nancy J.
Bankston, Laurie A.
Donis, Ruben O.
Liddington, Robert C.
Marasco, Wayne A.
author_role author
author2 Hwang, William C.
Perez, Sandra
Wei, Ge
Aird, Daniel
Chen, Li-Mei
Santelli, Eugenio
Stec, Boguslaw
Cadwell, Greg
Ali, Maryam
Wan, Hongquan
Murakami, Akikazu
Yammanuru, Anuradha
Han, Thomas
Cox, Nancy J.
Bankston, Laurie A.
Donis, Ruben O.
Liddington, Robert C.
Marasco, Wayne A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv INFLUENZA
MONOCLONAL ANTIBODIES
IMMUNOTHERAPY
H5N1
topic INFLUENZA
MONOCLONAL ANTIBODIES
IMMUNOTHERAPY
H5N1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.
Fil: Sui, Jianhua. Harvard Medical School; Estados Unidos. Dana-farber Cancer Institute; Estados Unidos
Fil: Hwang, William C.. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Perez, Sandra. National Center For Immunization And Respiratory Diseases; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wei, Ge. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Aird, Daniel. Harvard Medical School; Estados Unidos. Dana-farber Cancer Institute; Estados Unidos
Fil: Chen, Li-Mei. National Center For Immunization And Respiratory Diseases; Estados Unidos
Fil: Santelli, Eugenio. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Stec, Boguslaw. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Cadwell, Greg. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Ali, Maryam. Dana-farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Wan, Hongquan. National Center For Immunization And Respiratory Diseases; Estados Unidos
Fil: Murakami, Akikazu. Harvard Medical School; Estados Unidos. Dana-farber Cancer Institute; Estados Unidos
Fil: Yammanuru, Anuradha. Dana-farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados Unidos
Fil: Han, Thomas. Harvard Medical School; Estados Unidos. Dana-farber Cancer Institute; Estados Unidos
Fil: Cox, Nancy J.. National Center For Immunization And Respiratory Diseases; Estados Unidos
Fil: Bankston, Laurie A.. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Donis, Ruben O.. National Center For Immunization And Respiratory Diseases; Estados Unidos
Fil: Liddington, Robert C.. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos
Fil: Marasco, Wayne A.. Dana-farber Cancer Institute; Estados Unidos. Harvard Medical School; Estados Unidos
description Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.
publishDate 2009
dc.date.none.fl_str_mv 2009-03
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/11336/96252
Sui, Jianhua; Hwang, William C.; Perez, Sandra; Wei, Ge; Aird, Daniel; et al.; Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses; Nature Publishing Group; Nature Structural and Molecular Biology; 16; 3; 3-2009; 265-273
1072-8368
1545-9985
CONICET Digital
CONICET
url http://hdl.handle.net/11336/96252
identifier_str_mv Sui, Jianhua; Hwang, William C.; Perez, Sandra; Wei, Ge; Aird, Daniel; et al.; Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses; Nature Publishing Group; Nature Structural and Molecular Biology; 16; 3; 3-2009; 265-273
1072-8368
1545-9985
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/nsmb.1566
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nsmb.1566
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692245/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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
_version_ 1843605868732481536
score 13.001348

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