Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif

The HIV-1 gp41 Membrane Proximal External Region (MPER) is recognized by broadly neutralizing antibodies and represents a promising vaccine target. However, MPER immunogenicity and antibody activity are influenced by membrane lipids. To evaluate lipid modulation of MPER immunogenicity, we generated...

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Autores: Molinos Albert, Luis M., Bilbao, Eneritz, Agulló, Luis, Marfil, Silvia, García, Elisabet, Rodríguez de la Concepción, María Luisa, Izquierdo Useros, Nuria, Vilaplana, Cristina, Nieto Garai, Jon Ander, Contreras, F. Xabier, Floor, Martin, Cardona, Pere J., Martínez Picado, Javier, Clotet, Bonaventura, Villà Freixa, Jordi, Lorizate Nogales, Maier, Carillo, Jorge, Blanco, Julià
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/64374
Acceso en línea:http://hdl.handle.net/10810/64374
Access Level:acceso abierto
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oai_identifier_str oai:addi.ehu.eus:10810/64374
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network_name_str España
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dc.title.none.fl_str_mv Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif
title Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif
spellingShingle Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif
Molinos Albert, Luis M.
title_short Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif
title_full Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif
title_fullStr Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif
title_full_unstemmed Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif
title_sort Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif
dc.creator.none.fl_str_mv Molinos Albert, Luis M.
Bilbao, Eneritz
Agulló, Luis
Marfil, Silvia
García, Elisabet
Rodríguez de la Concepción, María Luisa
Izquierdo Useros, Nuria
Vilaplana, Cristina
Nieto Garai, Jon Ander
Contreras, F. Xabier
Floor, Martin
Cardona, Pere J.
Martínez Picado, Javier
Clotet, Bonaventura
Villà Freixa, Jordi
Lorizate Nogales, Maier
Carillo, Jorge
Blanco, Julià
author Molinos Albert, Luis M.
author_facet Molinos Albert, Luis M.
Bilbao, Eneritz
Agulló, Luis
Marfil, Silvia
García, Elisabet
Rodríguez de la Concepción, María Luisa
Izquierdo Useros, Nuria
Vilaplana, Cristina
Nieto Garai, Jon Ander
Contreras, F. Xabier
Floor, Martin
Cardona, Pere J.
Martínez Picado, Javier
Clotet, Bonaventura
Villà Freixa, Jordi
Lorizate Nogales, Maier
Carillo, Jorge
Blanco, Julià
author_role author
author2 Bilbao, Eneritz
Agulló, Luis
Marfil, Silvia
García, Elisabet
Rodríguez de la Concepción, María Luisa
Izquierdo Useros, Nuria
Vilaplana, Cristina
Nieto Garai, Jon Ander
Contreras, F. Xabier
Floor, Martin
Cardona, Pere J.
Martínez Picado, Javier
Clotet, Bonaventura
Villà Freixa, Jordi
Lorizate Nogales, Maier
Carillo, Jorge
Blanco, Julià
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
description The HIV-1 gp41 Membrane Proximal External Region (MPER) is recognized by broadly neutralizing antibodies and represents a promising vaccine target. However, MPER immunogenicity and antibody activity are influenced by membrane lipids. To evaluate lipid modulation of MPER immunogenicity, we generated a 1-Palmitoyl-2-oleoylphosphatidylcholine (POPC)-based proteoliposome collection containing combinations of phosphatidylserine (PS), GM3 ganglioside, cholesterol (CHOL), sphingomyelin (SM) and the TLR4 agonist monophosphoryl lipid A (MPLA). A recombinant gp41-derived miniprotein (gp41-MinTT) exposing the MPER and a tetanus toxoid (TT) peptide that favors MHC-II presentation, was successfully incorporated into lipid mixtures (>85%). Immunization of mice with soluble gp41-MinTT exclusively induced responses against the TT peptide, while POPC proteoliposomes generated potent anti-gp41 IgG responses using lower protein doses. The combined addition of PS and GM3 or CHOL/SM to POPC liposomes greatly increased gp41 immunogenicity, which was further enhanced by the addition of MPLA. Responses generated by all proteoliposomes targeted the N-terminal moiety of MPER overlapping the 2F5 neutralizing epitope. Our data show that lipids impact both, the epitope targeted and the magnitude of the response to membrane-dependent antigens, helping to improve MPER-based lipid carriers. Moreover, the identification of immunodominant epitopes allows for the redesign of immunogens targeting MPER neutralizing determinants.
publishDate 2017
dc.date.none.fl_str_mv 2017
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/64374
url http://hdl.handle.net/10810/64374
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.nature.com/articles/srep40800
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motifMolinos Albert, Luis M.Bilbao, EneritzAgulló, LuisMarfil, SilviaGarcía, ElisabetRodríguez de la Concepción, María LuisaIzquierdo Useros, NuriaVilaplana, CristinaNieto Garai, Jon AnderContreras, F. XabierFloor, MartinCardona, Pere J.Martínez Picado, JavierClotet, BonaventuraVillà Freixa, JordiLorizate Nogales, MaierCarillo, JorgeBlanco, JuliàThe HIV-1 gp41 Membrane Proximal External Region (MPER) is recognized by broadly neutralizing antibodies and represents a promising vaccine target. However, MPER immunogenicity and antibody activity are influenced by membrane lipids. To evaluate lipid modulation of MPER immunogenicity, we generated a 1-Palmitoyl-2-oleoylphosphatidylcholine (POPC)-based proteoliposome collection containing combinations of phosphatidylserine (PS), GM3 ganglioside, cholesterol (CHOL), sphingomyelin (SM) and the TLR4 agonist monophosphoryl lipid A (MPLA). A recombinant gp41-derived miniprotein (gp41-MinTT) exposing the MPER and a tetanus toxoid (TT) peptide that favors MHC-II presentation, was successfully incorporated into lipid mixtures (>85%). Immunization of mice with soluble gp41-MinTT exclusively induced responses against the TT peptide, while POPC proteoliposomes generated potent anti-gp41 IgG responses using lower protein doses. The combined addition of PS and GM3 or CHOL/SM to POPC liposomes greatly increased gp41 immunogenicity, which was further enhanced by the addition of MPLA. Responses generated by all proteoliposomes targeted the N-terminal moiety of MPER overlapping the 2F5 neutralizing epitope. Our data show that lipids impact both, the epitope targeted and the magnitude of the response to membrane-dependent antigens, helping to improve MPER-based lipid carriers. Moreover, the identification of immunodominant epitopes allows for the redesign of immunogens targeting MPER neutralizing determinants.We are grateful to Jorge Díaz, Vanessa García and Ismael Varela from the Animal Facility of IGTP for excellent technical assistance. This work was supported by the HIVACAT Program, the CERCA Program (Generalitat de Catalunya), the Spanish AIDS network ‘Red Temática Cooperativa de Investigación en SIDA’ (RD12/0017/0002), the Fondo de Investigaciones Sanitarias and FEDER “Fondo Europeo de Desarrollo Regional” (grant number PI14/01307, to JB), the Basque Country Government (grant number IT838-13 to ML) and the Spanish Ministry of Economy (BFU2012-33103 to ML and FXC; and SAF2013-49042-R to JMP and NIU). The utilization of supercomputational facilities was supported by The Spanish Supercomputing Network (grant numbers BCV-2015-2-0009 and BCV-2016-2-0005). J.B. is a researcher from Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol supported by the Health Department of the Catalan Government (Generalitat de Catalunya). LMM-A was supported by an FI predoctoral grant from Agència de Gestió d’Ajuts Universitaris i de Recerca from Generalitat de Catalunya and European Social Fund. JAN is supported by an FI predoctoral fellowship from the Basque Government. CV receives support from ISCIII-Subdirección General de Evaluación and Fondo-EU de Desarrollo Regional (FEDER) contract CP13/00174. CV and PJC are members of the CRP-TB (Group 17) of the Spanish Network CIBER Enfermedades Respiratorias. The following reagents were obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: Anti-HIV-1 gp41 Monoclonal (D50) (Cat# 11393); HIV-1 Consensus Subtype B Env Peptide Set (cat# 9480).202420242017info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/64374reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.nature.com/articles/srep40800info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/oai:addi.ehu.eus:10810/643742026-06-18T09:23:17Z
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