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Título:
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Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif
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Autor/a:
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Molinos-Albert, Luis M.; Bilbao, Eneritz; Agulló, Luis; Marfil, Sílvia; García, Elisabet; Rodríguez de la Concepción, Maria L.; Izquierdo Useros, Nuria; Vilaplana, Cristina; Nieto-Garai, Jon A.; Contreras, F. Xabier; Floor, Martin; Cardona, Pere J.; Martinez Picado, Francisco Javier; Clotet, Bonaventura; Villà-Freixa, Jordi; Lorizate, M.; Carrillo, Jorge; Blanco, Julià
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Otros autores:
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Universitat de Vic - Universitat Central de Catalunya. Departament de Biociències; Universitat de Vic - Universitat Central de Catalunya. Càtedra de la Sida i Malalties Relacionades |
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Notas:
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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. |
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Materia(s):
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-Sida -- Tractament
-VIH (Virus) |
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Derechos:
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Aquest document està subjecte a aquesta llicència Creative Commons
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
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Tipo de documento:
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Artículo
info:eu-repo/publishedVersion |
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Editor:
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Nature Publishing Group
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Compartir:
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