dc.contributor |
Universitat de Vic - Universitat Central de Catalunya. Departament de Biociències |
dc.contributor |
Universitat de Vic - Universitat Central de Catalunya. Càtedra de la Sida i Malalties Relacionades |
dc.contributor.author |
Molinos-Albert, Luis M. |
dc.contributor.author |
Bilbao, Eneritz |
dc.contributor.author |
Agulló, Luis |
dc.contributor.author |
Marfil, Sílvia |
dc.contributor.author |
García, Elisabet |
dc.contributor.author |
Rodríguez de la Concepción, Maria L. |
dc.contributor.author |
Izquierdo Useros, Nuria |
dc.contributor.author |
Vilaplana, Cristina |
dc.contributor.author |
Nieto-Garai, Jon A. |
dc.contributor.author |
Contreras, F. Xabier |
dc.contributor.author |
Floor, Martin |
dc.contributor.author |
Cardona, Pere J. |
dc.contributor.author |
Martinez Picado, Francisco Javier |
dc.contributor.author |
Clotet, Bonaventura |
dc.contributor.author |
Villà-Freixa, Jordi |
dc.contributor.author |
Lorizate, M. |
dc.contributor.author |
Carrillo, Jorge |
dc.contributor.author |
Blanco, Julià |
dc.date |
2017 |
dc.identifier |
Molinos-Albert, L., Bilbao, Eneritz, Agulló, Luis, Marfil, Silvia, García, Elisabet, Rodríguez de la Concepción, Maria Luisa, Izquierdo-Useros, Nuria, Vilaplana, Cristina, Contreras, F. Xabier, Floor, Martin, Cardona, Pere J., Martinez-Picado, Javier Clotet, Bonaventura Villà-Freixa, Jordi Lorizate, Maier Carrillo, Jorge Blanco Julià.. (2017). Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif. Scientific Reports., 7(40800) |
dc.identifier |
2045-2322 |
dc.identifier |
http://hdl.handle.net/10854/4867 |
dc.identifier |
https://doi.org/10.1038/srep40800 |
dc.identifier.uri |
http://hdl.handle.net/10854/4867 |
dc.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. |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
Nature Publishing Group |
dc.rights |
Aquest document està subjecte a aquesta llicència Creative Commons |
dc.rights |
http://creativecommons.org/licenses/by-nc-nd/3.0/es/ |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Sida -- Tractament |
dc.subject |
VIH (Virus) |
dc.title |
Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/publishedVersion |