Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals

Background The MPER region of the HIV-1 envelope glycoprotein gp41 is targeted by broadly neutralizing antibodies. However, the localization of this epitope in a hydrophobic environment seems to hamper the elicitation of these antibodies in HIV infected individuals. We have quantified and characteri...

Descripción completa

Detalles Bibliográficos
Autores: Molinos-Albert, Luis M., Carrillo, Jorge, Curriu, Marta, Rodríguez de la Concepción, Maria L., Marfil, Sílvia, García, Elisabet, Clotet, Bonaventura, Blanco, Julià
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:UVic-UCC
Repositorio:RiUVic. Repositori institucional de la UVic-UCC
OAI Identifier:oai:dspace.uvic.cat:10854/3232
Acceso en línea:http://dx.doi.org/10.1186/1742-4690-11-44
http://hdl.handle.net/10854/3232
Access Level:acceso abierto
Palabra clave:Sida -- Tractament
id ES_3577f2d177fdf7b4e75de53d5a85af77
oai_identifier_str oai:dspace.uvic.cat:10854/3232
network_acronym_str ES
network_name_str España
repository_id_str
spelling Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individualsMolinos-Albert, Luis M.Carrillo, JorgeCurriu, MartaRodríguez de la Concepción, Maria L.Marfil, SílviaGarcía, ElisabetClotet, BonaventuraBlanco, JuliàSida -- TractamentBackground The MPER region of the HIV-1 envelope glycoprotein gp41 is targeted by broadly neutralizing antibodies. However, the localization of this epitope in a hydrophobic environment seems to hamper the elicitation of these antibodies in HIV infected individuals. We have quantified and characterized anti-MPER antibodies by ELISA and by flow cytometry using a collection of mini gp41-derived proteins expressed on the surface of 293T cells. Longitudinal plasma samples from 35 HIV-1 infected individuals were assayed for MPER recognition and MPER-dependent neutralizing capacity using HIV-2 viruses engrafted with HIV-1 MPER sequences. Results Miniproteins devoid of the cysteine loop of gp41 exposed the MPER on 293T cell membrane. Anti-MPER antibodies were identified in most individuals and were stable when analyzed in longitudinal samples. The magnitude of the responses was strongly correlated with the global response to the HIV-1 envelope glycoprotein, suggesting no specific limitation for anti-MPER antibodies. Peptide mapping showed poor recognition of the C-terminal MPER moiety and a wide presence of antibodies against the 2F5 epitope. However, antibody titers failed to correlate with 2F5-blocking activity and, more importantly, with the specific neutralization of HIV-2 chimeric viruses bearing the HIV-1 MPER sequence; suggesting a strong functional heterogeneity in anti-MPER humoral responses. Conclusions Anti-MPER antibodies can be detected in the vast majority of HIV-1 infected individuals and are generated in the context of the global anti-Env response. However, the neutralizing capacity is heterogeneous suggesting that eliciting neutralizing anti-MPER antibodies by immunization might require refinement of immunogens to skip nonneutralizing responses.Biomed centralUniversitat de Vic - Universitat Central de Catalunya. Càtedra de la Sida i Malalties Relacionades2014201420142014info:eu-repo/semantics/articleinfo:eu-repo/publishedVersionapplication/pdf12 p.application/pdfhttp://dx.doi.org/10.1186/1742-4690-11-44http://hdl.handle.net/10854/3232reponame:RiUVic. Repositori institucional de la UVic-UCCinstname:UVic-UCCIngléshttp://www.retrovirology.com/content/11/1/44Aquest document està subjecte a aquesta llicència Creative Commonshttp://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:dspace.uvic.cat:10854/32322026-06-07T19:15:21Z
dc.title.none.fl_str_mv Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals
title Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals
spellingShingle Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals
Molinos-Albert, Luis M.
Sida -- Tractament
title_short Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals
title_full Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals
title_fullStr Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals
title_full_unstemmed Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals
title_sort Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals
dc.creator.none.fl_str_mv Molinos-Albert, Luis M.
Carrillo, Jorge
Curriu, Marta
Rodríguez de la Concepción, Maria L.
Marfil, Sílvia
García, Elisabet
Clotet, Bonaventura
Blanco, Julià
author Molinos-Albert, Luis M.
author_facet Molinos-Albert, Luis M.
Carrillo, Jorge
Curriu, Marta
Rodríguez de la Concepción, Maria L.
Marfil, Sílvia
García, Elisabet
Clotet, Bonaventura
Blanco, Julià
author_role author
author2 Carrillo, Jorge
Curriu, Marta
Rodríguez de la Concepción, Maria L.
Marfil, Sílvia
García, Elisabet
Clotet, Bonaventura
Blanco, Julià
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat de Vic - Universitat Central de Catalunya. Càtedra de la Sida i Malalties Relacionades
dc.subject.none.fl_str_mv Sida -- Tractament
topic Sida -- Tractament
description Background The MPER region of the HIV-1 envelope glycoprotein gp41 is targeted by broadly neutralizing antibodies. However, the localization of this epitope in a hydrophobic environment seems to hamper the elicitation of these antibodies in HIV infected individuals. We have quantified and characterized anti-MPER antibodies by ELISA and by flow cytometry using a collection of mini gp41-derived proteins expressed on the surface of 293T cells. Longitudinal plasma samples from 35 HIV-1 infected individuals were assayed for MPER recognition and MPER-dependent neutralizing capacity using HIV-2 viruses engrafted with HIV-1 MPER sequences. Results Miniproteins devoid of the cysteine loop of gp41 exposed the MPER on 293T cell membrane. Anti-MPER antibodies were identified in most individuals and were stable when analyzed in longitudinal samples. The magnitude of the responses was strongly correlated with the global response to the HIV-1 envelope glycoprotein, suggesting no specific limitation for anti-MPER antibodies. Peptide mapping showed poor recognition of the C-terminal MPER moiety and a wide presence of antibodies against the 2F5 epitope. However, antibody titers failed to correlate with 2F5-blocking activity and, more importantly, with the specific neutralization of HIV-2 chimeric viruses bearing the HIV-1 MPER sequence; suggesting a strong functional heterogeneity in anti-MPER humoral responses. Conclusions Anti-MPER antibodies can be detected in the vast majority of HIV-1 infected individuals and are generated in the context of the global anti-Env response. However, the neutralizing capacity is heterogeneous suggesting that eliciting neutralizing anti-MPER antibodies by immunization might require refinement of immunogens to skip nonneutralizing responses.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014
2014
2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/publishedVersion
format article
dc.identifier.none.fl_str_mv http://dx.doi.org/10.1186/1742-4690-11-44
http://hdl.handle.net/10854/3232
url http://dx.doi.org/10.1186/1742-4690-11-44
http://hdl.handle.net/10854/3232
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://www.retrovirology.com/content/11/1/44
dc.rights.none.fl_str_mv Aquest document està subjecte a aquesta llicència Creative Commons
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Aquest document està subjecte a aquesta llicència Creative Commons
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
12 p.
application/pdf
dc.publisher.none.fl_str_mv Biomed central
publisher.none.fl_str_mv Biomed central
dc.source.none.fl_str_mv reponame:RiUVic. Repositori institucional de la UVic-UCC
instname:UVic-UCC
instname_str UVic-UCC
reponame_str RiUVic. Repositori institucional de la UVic-UCC
collection RiUVic. Repositori institucional de la UVic-UCC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869405889773961216
score 15.300724

Similares en LA Referencia