Title |
Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif
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Published in |
Scientific Reports, January 2017
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DOI | 10.1038/srep40800 |
Pubmed ID | |
Authors |
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, Julià Blanco |
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, 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Spain | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 50% |
Scientists | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 52 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 14 | 27% |
Student > Master | 8 | 15% |
Student > Ph. D. Student | 7 | 13% |
Professor | 6 | 12% |
Professor > Associate Professor | 3 | 6% |
Other | 7 | 13% |
Unknown | 7 | 13% |
Readers by discipline | Count | As % |
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Immunology and Microbiology | 9 | 17% |
Medicine and Dentistry | 8 | 15% |
Biochemistry, Genetics and Molecular Biology | 7 | 13% |
Agricultural and Biological Sciences | 7 | 13% |
Chemistry | 4 | 8% |
Other | 7 | 13% |
Unknown | 10 | 19% |