Web of Science: 5 citations, Scopus: 5 citations, Google Scholar: citations,
Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif
Molinos-Albert, Luis Manuel (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Bilbao, Eneritz (Universidad del País Vasco (UPV/EHU). Department of Biochemistry and Molecular Biology)
Agulló, Luis (Universitat de Vic. Departament de Biociències)
Marfil, Silvia (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
García, Elisabet (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Rodríguez de la Concepción, Maria Luisa (Institut Germans Trias i Pujol)
Izquierdo-Useros, Nuria (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Vilaplana, Cristina (Institut Germans Trias i Pujol. Unitat de Tuberculosi Experimental)
Nieto-Garai, Jon A. (Universidad del País Vasco (UPV/EHU). Department of Biochemistry and Molecular Biology)
Contreras, F. Xabier (Universidad del País Vasco (UPV/EHU). Department of Biochemistry and Molecular Biology)
Floor, Martin (Universitat de Vic. Departament de Biociències)
Cardona, Pere J. (Institut Germans Trias i Pujol. Unitat de Tuberculosi Experimental)
Martínez Picado, Francisco Javier (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Clotet, Bonaventura (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Villà-Freixa, Jordi (Universitat de Vic. Departament de Biociències)
Lorizate, Maier (Universidad del País Vasco (UPV/EHU). Department of Biochemistry and Molecular Biology)
Carrillo, Jorge (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Blanco, Julià (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)

Date: 2017
Abstract: 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, holesterol (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.
Note: Número d'acord de subvenció FIS/PI14/01307
Note: Número d'acord de subvenció MINECO/BFU2012-33103
Note: Número d'acord de subvenció MINECO/SAF2013-49042-R
Note: Número d'acord de subvenció ISCIII/CP13/00174
Note: Altres ajuts: Programa HIVACAT, programa CERCA (Generalitat de Catalunya), Red Temática Cooperativa de Investigación en SIDA (RD12/0017/0002)), Govern Basc (IT838-13), Spanish Supercomputing Network (grant numbers BCV-2015-2-0009 and BCV-2016-2-0005)
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Published in: Scientific Reports, gener 2017, p. 1-15

DOI: 10.1038/srep40800
PMID: 28084464


15 p, 2.1 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles

 Record created 2018-10-05, last modified 2019-10-02



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