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

Overview of attention for article published in Scientific Reports, January 2017
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Title
Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif
Published in
Scientific Reports, January 2017
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.

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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
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 %
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%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 January 2017.
All research outputs
#14,908,193
of 22,940,083 outputs
Outputs from Scientific Reports
#72,681
of 123,872 outputs
Outputs of similar age
#243,528
of 421,590 outputs
Outputs of similar age from Scientific Reports
#2,284
of 3,808 outputs
Altmetric has tracked 22,940,083 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 123,872 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.2. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 421,590 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3,808 others from the same source and published within six weeks on either side of this one. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.