Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1

Autores
McCoy, Laura E.; Rutten, Lucy; Frampton, Dan; Anderson, Ian; Granger, Luke; Bashford Rogers, Rachael; Dekkers, Gillian; Strokappe, Nika M.; Seaman, Michael S.; Koh, Willie; Grippo, Vanina; Kliche, Alexander; Verrips, Theo; Kellam, Paul; Fassati, Ariberto; Weiss, Robin A.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.
Fil: McCoy, Laura E.. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Fil: Rutten, Lucy. QVQ B.V.; Países Bajos
Fil: Frampton, Dan. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Fil: Anderson, Ian. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Fil: Granger, Luke. King’s College London. School of Medicine. Guy’s Hospital. Department of Infectious Diseases; Reino Unido
Fil: Bashford Rogers, Rachael. Wellcome Trust Sanger Institute; Reino Unido
Fil: Dekkers, Gillian. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Fil: Strokappe, Nika M.. QVQ B.V.; Países Bajos
Fil: Seaman, Michael S.. Harvard Medical School. Beth Israel Deaconess Medical Center. Center for Virology and Vaccine Research; Estados Unidos
Fil: Koh, Willie. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Fil: Grippo, Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencias y Tecnología "Dr. Cesar Milstein"; Argentina
Fil: Kliche, Alexander. University of Regensburg. Institute of Medical Microbiology; Alemania
Fil: Verrips, Theo. QVQ B.V.; Países Bajos
Fil: Kellam, Paul. Wellcome Trust Sanger Institute; Reino Unido
Fil: Fassati, Ariberto. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Fil: Weiss, Robin A.. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Materia
Neutralizing Llama antibodies
HIV-1
CD4-Binding Site
Molecular evolution
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:11336/4155
Acceder
id CONICETDig_1fbc98f09e6acfe3d91b48908a86bd63
oai_identifier_str oai:ri.conicet.gov.ar:11336/4155
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1McCoy, Laura E.Rutten, LucyFrampton, DanAnderson, IanGranger, LukeBashford Rogers, RachaelDekkers, GillianStrokappe, Nika M.Seaman, Michael S.Koh, WillieGrippo, VaninaKliche, AlexanderVerrips, TheoKellam, PaulFassati, AribertoWeiss, Robin A.Neutralizing Llama antibodiesHIV-1CD4-Binding SiteMolecular evolutionhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.Fil: McCoy, Laura E.. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino UnidoFil: Rutten, Lucy. QVQ B.V.; Países BajosFil: Frampton, Dan. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino UnidoFil: Anderson, Ian. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino UnidoFil: Granger, Luke. King’s College London. School of Medicine. Guy’s Hospital. Department of Infectious Diseases; Reino UnidoFil: Bashford Rogers, Rachael. Wellcome Trust Sanger Institute; Reino UnidoFil: Dekkers, Gillian. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino UnidoFil: Strokappe, Nika M.. QVQ B.V.; Países BajosFil: Seaman, Michael S.. Harvard Medical School. Beth Israel Deaconess Medical Center. Center for Virology and Vaccine Research; Estados UnidosFil: Koh, Willie. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino UnidoFil: Grippo, Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencias y Tecnología "Dr. Cesar Milstein"; ArgentinaFil: Kliche, Alexander. University of Regensburg. Institute of Medical Microbiology; AlemaniaFil: Verrips, Theo. QVQ B.V.; Países BajosFil: Kellam, Paul. Wellcome Trust Sanger Institute; Reino UnidoFil: Fassati, Ariberto. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino UnidoFil: Weiss, Robin A.. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino UnidoPublic Library of Science2014-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/4155McCoy, Laura E.; Rutten, Lucy; Frampton, Dan; Anderson, Ian; Granger, Luke; et al.; Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1; Public Library of Science; Plos Pathogens; 10; 12; 12-2014; e1004552-e10045521553-7366enginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004552info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/DOI:10.1371/journal.ppat.1004552info:eu-repo/semantics/altIdentifier/issn/1553-7366info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pubmed/25522326info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:54:20Zoai:ri.conicet.gov.ar:11336/4155instacron: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 09:54:20.828CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1
title Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1
spellingShingle Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1
McCoy, Laura E.
Neutralizing Llama antibodies
HIV-1
CD4-Binding Site
Molecular evolution
title_short Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1
title_full Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1
title_fullStr Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1
title_full_unstemmed Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1
title_sort Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1
dc.creator.none.fl_str_mv McCoy, Laura E.
Rutten, Lucy
Frampton, Dan
Anderson, Ian
Granger, Luke
Bashford Rogers, Rachael
Dekkers, Gillian
Strokappe, Nika M.
Seaman, Michael S.
Koh, Willie
Grippo, Vanina
Kliche, Alexander
Verrips, Theo
Kellam, Paul
Fassati, Ariberto
Weiss, Robin A.
author McCoy, Laura E.
author_facet McCoy, Laura E.
Rutten, Lucy
Frampton, Dan
Anderson, Ian
Granger, Luke
Bashford Rogers, Rachael
Dekkers, Gillian
Strokappe, Nika M.
Seaman, Michael S.
Koh, Willie
Grippo, Vanina
Kliche, Alexander
Verrips, Theo
Kellam, Paul
Fassati, Ariberto
Weiss, Robin A.
author_role author
author2 Rutten, Lucy
Frampton, Dan
Anderson, Ian
Granger, Luke
Bashford Rogers, Rachael
Dekkers, Gillian
Strokappe, Nika M.
Seaman, Michael S.
Koh, Willie
Grippo, Vanina
Kliche, Alexander
Verrips, Theo
Kellam, Paul
Fassati, Ariberto
Weiss, Robin A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Neutralizing Llama antibodies
HIV-1
CD4-Binding Site
Molecular evolution
topic Neutralizing Llama antibodies
HIV-1
CD4-Binding Site
Molecular evolution
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.
Fil: McCoy, Laura E.. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Fil: Rutten, Lucy. QVQ B.V.; Países Bajos
Fil: Frampton, Dan. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Fil: Anderson, Ian. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Fil: Granger, Luke. King’s College London. School of Medicine. Guy’s Hospital. Department of Infectious Diseases; Reino Unido
Fil: Bashford Rogers, Rachael. Wellcome Trust Sanger Institute; Reino Unido
Fil: Dekkers, Gillian. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Fil: Strokappe, Nika M.. QVQ B.V.; Países Bajos
Fil: Seaman, Michael S.. Harvard Medical School. Beth Israel Deaconess Medical Center. Center for Virology and Vaccine Research; Estados Unidos
Fil: Koh, Willie. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Fil: Grippo, Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencias y Tecnología "Dr. Cesar Milstein"; Argentina
Fil: Kliche, Alexander. University of Regensburg. Institute of Medical Microbiology; Alemania
Fil: Verrips, Theo. QVQ B.V.; Países Bajos
Fil: Kellam, Paul. Wellcome Trust Sanger Institute; Reino Unido
Fil: Fassati, Ariberto. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
Fil: Weiss, Robin A.. University College London. Division of Infection and Immunity. Centre for Medical Molecular Virology. Wohl Virion Centre and Medical Research Council; Reino Unido
description To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.
publishDate 2014
dc.date.none.fl_str_mv 2014-12
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/11336/4155
McCoy, Laura E.; Rutten, Lucy; Frampton, Dan; Anderson, Ian; Granger, Luke; et al.; Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1; Public Library of Science; Plos Pathogens; 10; 12; 12-2014; e1004552-e1004552
1553-7366
url http://hdl.handle.net/11336/4155
identifier_str_mv McCoy, Laura E.; Rutten, Lucy; Frampton, Dan; Anderson, Ian; Granger, Luke; et al.; Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1; Public Library of Science; Plos Pathogens; 10; 12; 12-2014; e1004552-e1004552
1553-7366
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004552
info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/DOI:10.1371/journal.ppat.1004552
info:eu-repo/semantics/altIdentifier/issn/1553-7366
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pubmed/25522326
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 Public Library of Science
publisher.none.fl_str_mv Public Library 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)
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_ 1842269280221003776
score 13.13397

Publicaciones similares