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

Luis M. Molinos-Albert, Eneritz Bilbao, Luis Agulló, Silvia Marfil, Elisabet García, Maria Luisa Rodríguez De La Concepción, Nuria Izquierdo-Useros, Cristina Vilaplana, Jon A. Nieto-Garai, F. Xabier Contreras, Martin Floor, Pere J. Cardona, Javier Martinez-Picado, Bonaventura Clotet, Jordi Villà-Freixa, Maier Lorizate, Jorge Carrillo, Julia Blanco

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

© The Author(s) 2017. 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.
Original languageEnglish
Article number40800
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 13 Jan 2017

Fingerprint Dive into the research topics of 'Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif'. Together they form a unique fingerprint.

Cite this