Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease
- Autores
- Delgado, Maria Florencia; Coviello, Silvina Andrea; Monsalvo, Ana Clara; Melendi, Guillermina Amanda; Hernandez, Johanna Zea; Batalle, Juan Pio; Diaz, Leandro; Trento, Alfonsina; Chang, Herng-Yu; Mitzner, Wayne; Ravetch, Jeffrey; Melero, José A.; Irusta, Pablo M.; Polack, Fernando Pedro
- Año de publicación
- 2009
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants. A formalin-inactivated RSV vaccine was used to immunize children and elicited nonprotective, pathogenic antibody. Immunized infants experienced increased morbidity after subsequent RSV exposure. No vaccine has been licensed since that time. A widely accepted hypothesis attributed the vaccine failure to formalin disruption of protective antigens. Here we show that the lack of protection was not due to alterations caused by formalin but instead to low antibody avidity for protective epitopes. Lack of antibody affinity maturation followed poor Toll-like receptor (TLR) stimulation. This study explains why the inactivated RSV vaccine did not protect the children and consequently led to severe disease, hampering vaccine development for 42 years. It also suggests that inactivated RSV vaccines may be rendered safe and effective by inclusion of TLR agonists in their formulation, and it identifies affinity maturation as a key factor for the safe immunization of infants.
Fil: Delgado, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Monsalvo, Ana Clara. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Melendi, Guillermina Amanda. Fundación para la Investigación en Infectología Infantil; Argentina. University Johns Hopkins; Estados Unidos
Fil: Hernandez, Johanna Zea. Fundación para la Investigación en Infectología Infantil; Argentina. University Johns Hopkins; Estados Unidos
Fil: Batalle, Juan Pio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Diaz, Leandro. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Trento, Alfonsina. Universidad Carlos III de Madrid. Instituto de Salud; España
Fil: Chang, Herng-Yu. University Johns Hopkins; Estados Unidos
Fil: Mitzner, Wayne. University Johns Hopkins; Estados Unidos
Fil: Ravetch, Jeffrey. The Rockefeller University; Estados Unidos
Fil: Melero, José A.. Universidad Carlos III de Madrid. Instituto de Salud; España
Fil: Irusta, Pablo M.. University Of Georgetown; Estados Unidos. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. University Johns Hopkins; Estados Unidos - Materia
-
RSV
FIRSV
TLR
Antibodies - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/96246
Ver los metadatos del registro completo
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Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus diseaseDelgado, Maria FlorenciaCoviello, Silvina AndreaMonsalvo, Ana ClaraMelendi, Guillermina AmandaHernandez, Johanna ZeaBatalle, Juan PioDiaz, LeandroTrento, AlfonsinaChang, Herng-YuMitzner, WayneRavetch, JeffreyMelero, José A.Irusta, Pablo M.Polack, Fernando PedroRSVFIRSVTLRAntibodieshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants. A formalin-inactivated RSV vaccine was used to immunize children and elicited nonprotective, pathogenic antibody. Immunized infants experienced increased morbidity after subsequent RSV exposure. No vaccine has been licensed since that time. A widely accepted hypothesis attributed the vaccine failure to formalin disruption of protective antigens. Here we show that the lack of protection was not due to alterations caused by formalin but instead to low antibody avidity for protective epitopes. Lack of antibody affinity maturation followed poor Toll-like receptor (TLR) stimulation. This study explains why the inactivated RSV vaccine did not protect the children and consequently led to severe disease, hampering vaccine development for 42 years. It also suggests that inactivated RSV vaccines may be rendered safe and effective by inclusion of TLR agonists in their formulation, and it identifies affinity maturation as a key factor for the safe immunization of infants.Fil: Delgado, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Monsalvo, Ana Clara. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Melendi, Guillermina Amanda. Fundación para la Investigación en Infectología Infantil; Argentina. University Johns Hopkins; Estados UnidosFil: Hernandez, Johanna Zea. Fundación para la Investigación en Infectología Infantil; Argentina. University Johns Hopkins; Estados UnidosFil: Batalle, Juan Pio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Diaz, Leandro. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Trento, Alfonsina. Universidad Carlos III de Madrid. Instituto de Salud; EspañaFil: Chang, Herng-Yu. University Johns Hopkins; Estados UnidosFil: Mitzner, Wayne. University Johns Hopkins; Estados UnidosFil: Ravetch, Jeffrey. The Rockefeller University; Estados UnidosFil: Melero, José A.. Universidad Carlos III de Madrid. Instituto de Salud; EspañaFil: Irusta, Pablo M.. University Of Georgetown; Estados Unidos. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. University Johns Hopkins; Estados UnidosNature Publishing Group2009-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96246Delgado, Maria Florencia; Coviello, Silvina Andrea; Monsalvo, Ana Clara; Melendi, Guillermina Amanda; Hernandez, Johanna Zea; et al.; Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease; Nature Publishing Group; Nature Medicine; 15; 1; 1-2009; 34-411078-8956CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nm.1894info:eu-repo/semantics/altIdentifier/doi/10.1038/nm.1894info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:09:26Zoai:ri.conicet.gov.ar:11336/96246instacron: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 10:09:26.671CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease |
title |
Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease |
spellingShingle |
Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease Delgado, Maria Florencia RSV FIRSV TLR Antibodies |
title_short |
Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease |
title_full |
Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease |
title_fullStr |
Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease |
title_full_unstemmed |
Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease |
title_sort |
Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease |
dc.creator.none.fl_str_mv |
Delgado, Maria Florencia Coviello, Silvina Andrea Monsalvo, Ana Clara Melendi, Guillermina Amanda Hernandez, Johanna Zea Batalle, Juan Pio Diaz, Leandro Trento, Alfonsina Chang, Herng-Yu Mitzner, Wayne Ravetch, Jeffrey Melero, José A. Irusta, Pablo M. Polack, Fernando Pedro |
author |
Delgado, Maria Florencia |
author_facet |
Delgado, Maria Florencia Coviello, Silvina Andrea Monsalvo, Ana Clara Melendi, Guillermina Amanda Hernandez, Johanna Zea Batalle, Juan Pio Diaz, Leandro Trento, Alfonsina Chang, Herng-Yu Mitzner, Wayne Ravetch, Jeffrey Melero, José A. Irusta, Pablo M. Polack, Fernando Pedro |
author_role |
author |
author2 |
Coviello, Silvina Andrea Monsalvo, Ana Clara Melendi, Guillermina Amanda Hernandez, Johanna Zea Batalle, Juan Pio Diaz, Leandro Trento, Alfonsina Chang, Herng-Yu Mitzner, Wayne Ravetch, Jeffrey Melero, José A. Irusta, Pablo M. Polack, Fernando Pedro |
author2_role |
author author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
RSV FIRSV TLR Antibodies |
topic |
RSV FIRSV TLR Antibodies |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants. A formalin-inactivated RSV vaccine was used to immunize children and elicited nonprotective, pathogenic antibody. Immunized infants experienced increased morbidity after subsequent RSV exposure. No vaccine has been licensed since that time. A widely accepted hypothesis attributed the vaccine failure to formalin disruption of protective antigens. Here we show that the lack of protection was not due to alterations caused by formalin but instead to low antibody avidity for protective epitopes. Lack of antibody affinity maturation followed poor Toll-like receptor (TLR) stimulation. This study explains why the inactivated RSV vaccine did not protect the children and consequently led to severe disease, hampering vaccine development for 42 years. It also suggests that inactivated RSV vaccines may be rendered safe and effective by inclusion of TLR agonists in their formulation, and it identifies affinity maturation as a key factor for the safe immunization of infants. Fil: Delgado, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Monsalvo, Ana Clara. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Melendi, Guillermina Amanda. Fundación para la Investigación en Infectología Infantil; Argentina. University Johns Hopkins; Estados Unidos Fil: Hernandez, Johanna Zea. Fundación para la Investigación en Infectología Infantil; Argentina. University Johns Hopkins; Estados Unidos Fil: Batalle, Juan Pio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Diaz, Leandro. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Trento, Alfonsina. Universidad Carlos III de Madrid. Instituto de Salud; España Fil: Chang, Herng-Yu. University Johns Hopkins; Estados Unidos Fil: Mitzner, Wayne. University Johns Hopkins; Estados Unidos Fil: Ravetch, Jeffrey. The Rockefeller University; Estados Unidos Fil: Melero, José A.. Universidad Carlos III de Madrid. Instituto de Salud; España Fil: Irusta, Pablo M.. University Of Georgetown; Estados Unidos. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. University Johns Hopkins; Estados Unidos |
description |
Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants. A formalin-inactivated RSV vaccine was used to immunize children and elicited nonprotective, pathogenic antibody. Immunized infants experienced increased morbidity after subsequent RSV exposure. No vaccine has been licensed since that time. A widely accepted hypothesis attributed the vaccine failure to formalin disruption of protective antigens. Here we show that the lack of protection was not due to alterations caused by formalin but instead to low antibody avidity for protective epitopes. Lack of antibody affinity maturation followed poor Toll-like receptor (TLR) stimulation. This study explains why the inactivated RSV vaccine did not protect the children and consequently led to severe disease, hampering vaccine development for 42 years. It also suggests that inactivated RSV vaccines may be rendered safe and effective by inclusion of TLR agonists in their formulation, and it identifies affinity maturation as a key factor for the safe immunization of infants. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-01 |
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/11336/96246 Delgado, Maria Florencia; Coviello, Silvina Andrea; Monsalvo, Ana Clara; Melendi, Guillermina Amanda; Hernandez, Johanna Zea; et al.; Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease; Nature Publishing Group; Nature Medicine; 15; 1; 1-2009; 34-41 1078-8956 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/96246 |
identifier_str_mv |
Delgado, Maria Florencia; Coviello, Silvina Andrea; Monsalvo, Ana Clara; Melendi, Guillermina Amanda; Hernandez, Johanna Zea; et al.; Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease; Nature Publishing Group; Nature Medicine; 15; 1; 1-2009; 34-41 1078-8956 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://www.nature.com/articles/nm.1894 info:eu-repo/semantics/altIdentifier/doi/10.1038/nm.1894 |
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 |
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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