Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion

Autores
Schepens, Bert; Ibañez, Lorena Itatí; De Baets, Sarah; Hultberg, Anna; Bogaert, Pieter; De Bleser, Pieter; Vervalle, Frederik; Verrips, Theo; Melero, José; Vandevelde, Wesly; Vanlandschoot, Peter; Saelens, Xavier
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Despite the medical importance of respiratory syncytial virus (RSV) infections, there is no vaccine or therapeutic agent available. Prophylactic administration of palivizumab, a humanized monoclonal RSV fusion (F) protein-specific antibody, can protect high-risk children. Previously, we have demonstrated that RSV can be neutralized by picomolar concentrations of a camelid immunoglobulin single-variable domain that binds the RSV protein F (F-VHHb nanobodies). Here, we investigated the mechanism by which these nanobodies neutralize RSV and tested their antiviral activity in vivo. We demonstrate that bivalent RSV F-specific nanobodies neutralize RSV infection by inhibiting fusion without affecting viral attachment. The ability of RSV F-specific nanobodies to protect against RSV infection was investigated in vivo. Intranasal administration of bivalent RSV F-specific nanobodies protected BALB/c mice from RSV infection, and associated pulmonary inflammation. Moreover, therapeutic treatment with these nanobodies after RSV infection could reduce viral replication and reduced pulmonary inflammation. Thus, nanobodies are promising therapeutic molecules for treatment of RSV.
Fil: Schepens, Bert. University of Ghent; Bélgica
Fil: Ibañez, Lorena Itatí. University of Ghent; Bélgica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: De Baets, Sarah. University of Ghent; Bélgica
Fil: Hultberg, Anna. University of Utrecht; Países Bajos. Utrecht University; Países Bajos
Fil: Bogaert, Pieter. University of Ghent; Bélgica
Fil: De Bleser, Pieter. University of Ghent; Bélgica
Fil: Vervalle, Frederik. University of Ghent; Bélgica
Fil: Verrips, Theo. University of Utrecht; Países Bajos. Utrecht University; Países Bajos
Fil: Melero, José. No especifíca;
Fil: Vandevelde, Wesly. No especifíca;
Fil: Vanlandschoot, Peter. No especifíca;
Fil: Saelens, Xavier. University of Ghent; Bélgica
Materia
NANOBODY
ANTIVIRAL
RSV
CAMELID
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:11336/194183
Acceder
id CONICETDig_acae315f6128ac4cf3ca6ed72b7d20b2
oai_identifier_str oai:ri.conicet.gov.ar:11336/194183
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusionSchepens, BertIbañez, Lorena ItatíDe Baets, SarahHultberg, AnnaBogaert, PieterDe Bleser, PieterVervalle, FrederikVerrips, TheoMelero, JoséVandevelde, WeslyVanlandschoot, PeterSaelens, XavierNANOBODYANTIVIRALRSVCAMELIDhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/2https://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Despite the medical importance of respiratory syncytial virus (RSV) infections, there is no vaccine or therapeutic agent available. Prophylactic administration of palivizumab, a humanized monoclonal RSV fusion (F) protein-specific antibody, can protect high-risk children. Previously, we have demonstrated that RSV can be neutralized by picomolar concentrations of a camelid immunoglobulin single-variable domain that binds the RSV protein F (F-VHHb nanobodies). Here, we investigated the mechanism by which these nanobodies neutralize RSV and tested their antiviral activity in vivo. We demonstrate that bivalent RSV F-specific nanobodies neutralize RSV infection by inhibiting fusion without affecting viral attachment. The ability of RSV F-specific nanobodies to protect against RSV infection was investigated in vivo. Intranasal administration of bivalent RSV F-specific nanobodies protected BALB/c mice from RSV infection, and associated pulmonary inflammation. Moreover, therapeutic treatment with these nanobodies after RSV infection could reduce viral replication and reduced pulmonary inflammation. Thus, nanobodies are promising therapeutic molecules for treatment of RSV.Fil: Schepens, Bert. University of Ghent; BélgicaFil: Ibañez, Lorena Itatí. University of Ghent; Bélgica. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: De Baets, Sarah. University of Ghent; BélgicaFil: Hultberg, Anna. University of Utrecht; Países Bajos. Utrecht University; Países BajosFil: Bogaert, Pieter. University of Ghent; BélgicaFil: De Bleser, Pieter. University of Ghent; BélgicaFil: Vervalle, Frederik. University of Ghent; BélgicaFil: Verrips, Theo. University of Utrecht; Países Bajos. Utrecht University; Países BajosFil: Melero, José. No especifíca;Fil: Vandevelde, Wesly. No especifíca;Fil: Vanlandschoot, Peter. No especifíca;Fil: Saelens, Xavier. University of Ghent; BélgicaUniversity of Chicago Press2011-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/194183Schepens, Bert; Ibañez, Lorena Itatí; De Baets, Sarah; Hultberg, Anna; Bogaert, Pieter; et al.; Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion; University of Chicago Press; Journal Of Infectious Diseases; 204; 11; 12-2011; 1692-17010022-1899CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jid/article/204/11/1692/848267info:eu-repo/semantics/altIdentifier/doi/10.1093/infdis/jir622info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:00:58Zoai:ri.conicet.gov.ar:11336/194183instacron: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 10:00:58.481CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion
title Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion
spellingShingle Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion
Schepens, Bert
NANOBODY
ANTIVIRAL
RSV
CAMELID
title_short Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion
title_full Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion
title_fullStr Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion
title_full_unstemmed Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion
title_sort Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion
dc.creator.none.fl_str_mv Schepens, Bert
Ibañez, Lorena Itatí
De Baets, Sarah
Hultberg, Anna
Bogaert, Pieter
De Bleser, Pieter
Vervalle, Frederik
Verrips, Theo
Melero, José
Vandevelde, Wesly
Vanlandschoot, Peter
Saelens, Xavier
author Schepens, Bert
author_facet Schepens, Bert
Ibañez, Lorena Itatí
De Baets, Sarah
Hultberg, Anna
Bogaert, Pieter
De Bleser, Pieter
Vervalle, Frederik
Verrips, Theo
Melero, José
Vandevelde, Wesly
Vanlandschoot, Peter
Saelens, Xavier
author_role author
author2 Ibañez, Lorena Itatí
De Baets, Sarah
Hultberg, Anna
Bogaert, Pieter
De Bleser, Pieter
Vervalle, Frederik
Verrips, Theo
Melero, José
Vandevelde, Wesly
Vanlandschoot, Peter
Saelens, Xavier
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NANOBODY
ANTIVIRAL
RSV
CAMELID
topic NANOBODY
ANTIVIRAL
RSV
CAMELID
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Despite the medical importance of respiratory syncytial virus (RSV) infections, there is no vaccine or therapeutic agent available. Prophylactic administration of palivizumab, a humanized monoclonal RSV fusion (F) protein-specific antibody, can protect high-risk children. Previously, we have demonstrated that RSV can be neutralized by picomolar concentrations of a camelid immunoglobulin single-variable domain that binds the RSV protein F (F-VHHb nanobodies). Here, we investigated the mechanism by which these nanobodies neutralize RSV and tested their antiviral activity in vivo. We demonstrate that bivalent RSV F-specific nanobodies neutralize RSV infection by inhibiting fusion without affecting viral attachment. The ability of RSV F-specific nanobodies to protect against RSV infection was investigated in vivo. Intranasal administration of bivalent RSV F-specific nanobodies protected BALB/c mice from RSV infection, and associated pulmonary inflammation. Moreover, therapeutic treatment with these nanobodies after RSV infection could reduce viral replication and reduced pulmonary inflammation. Thus, nanobodies are promising therapeutic molecules for treatment of RSV.
Fil: Schepens, Bert. University of Ghent; Bélgica
Fil: Ibañez, Lorena Itatí. University of Ghent; Bélgica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: De Baets, Sarah. University of Ghent; Bélgica
Fil: Hultberg, Anna. University of Utrecht; Países Bajos. Utrecht University; Países Bajos
Fil: Bogaert, Pieter. University of Ghent; Bélgica
Fil: De Bleser, Pieter. University of Ghent; Bélgica
Fil: Vervalle, Frederik. University of Ghent; Bélgica
Fil: Verrips, Theo. University of Utrecht; Países Bajos. Utrecht University; Países Bajos
Fil: Melero, José. No especifíca;
Fil: Vandevelde, Wesly. No especifíca;
Fil: Vanlandschoot, Peter. No especifíca;
Fil: Saelens, Xavier. University of Ghent; Bélgica
description Despite the medical importance of respiratory syncytial virus (RSV) infections, there is no vaccine or therapeutic agent available. Prophylactic administration of palivizumab, a humanized monoclonal RSV fusion (F) protein-specific antibody, can protect high-risk children. Previously, we have demonstrated that RSV can be neutralized by picomolar concentrations of a camelid immunoglobulin single-variable domain that binds the RSV protein F (F-VHHb nanobodies). Here, we investigated the mechanism by which these nanobodies neutralize RSV and tested their antiviral activity in vivo. We demonstrate that bivalent RSV F-specific nanobodies neutralize RSV infection by inhibiting fusion without affecting viral attachment. The ability of RSV F-specific nanobodies to protect against RSV infection was investigated in vivo. Intranasal administration of bivalent RSV F-specific nanobodies protected BALB/c mice from RSV infection, and associated pulmonary inflammation. Moreover, therapeutic treatment with these nanobodies after RSV infection could reduce viral replication and reduced pulmonary inflammation. Thus, nanobodies are promising therapeutic molecules for treatment of RSV.
publishDate 2011
dc.date.none.fl_str_mv 2011-12
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/11336/194183
Schepens, Bert; Ibañez, Lorena Itatí; De Baets, Sarah; Hultberg, Anna; Bogaert, Pieter; et al.; Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion; University of Chicago Press; Journal Of Infectious Diseases; 204; 11; 12-2011; 1692-1701
0022-1899
CONICET Digital
CONICET
url http://hdl.handle.net/11336/194183
identifier_str_mv Schepens, Bert; Ibañez, Lorena Itatí; De Baets, Sarah; Hultberg, Anna; Bogaert, Pieter; et al.; Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion; University of Chicago Press; Journal Of Infectious Diseases; 204; 11; 12-2011; 1692-1701
0022-1899
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jid/article/204/11/1692/848267
info:eu-repo/semantics/altIdentifier/doi/10.1093/infdis/jir622
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 University of Chicago Press
publisher.none.fl_str_mv University of Chicago Press
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_ 1842269667918348288
score 13.13397

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