Confocal microscopy of giant vesicles supports the absence of HIV-1 neutralizing 2F5 antibody reactivity to plasma membrane phospholipids |
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Authors: | Beatriz Apellaniz Nerea Huarte Karola Vorauer-Uhl Petra Schwille |
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Affiliation: | a Biophysics Unit (CSIC-UPV/EHU), Biochemistry and Molecular Biology Department, University of the Basque Country, Bilbao, Spain b Biotechnologisches Zentrum der Technische Universität Dresden, 1307 Dresden, Germany c Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Austria |
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Abstract: | The broadly neutralizing anti-HIV-1 2F5 monoclonal antibody recognizes a gp41 epitope proximal to the viral membrane. Potential phospholipid autoreactivity at cell surfaces has raised concerns about the use of this antibody for development of vaccines or immunotherapy. In this study, confocal microscopy of giant unilamellar vesicles (GUVs) was used to assess 2F5 reactivity with phospholipids assembled into bilayers with surface charge and curvature stress approximating those of the eukaryotic plasma membranes. Antibody partitioning into lipid bilayers required the specific recognition of membrane-inserted epitope, indicating that 2F5 was unable to directly react with GUV phospholipids, even under fluid phase segregation conditions. Our results thus support the feasibility of raising 2F5-like neutralizing responses through vaccination, and the medical safety of mAb infusions. |
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Keywords: | Chol, cholesterol DiD, 1,19-dioctadecyl-3,3,39,39-tetramethylindodicarbocyanine perchlorate DiO, 1,1&prime -dioctadecyl-3,3&prime -oxacarbocyanine perchlorate DOPC, dioleoyl-phosphatidylcholine GUV, giant unilamellar vesicle MLV, multilamellar vesicle MPER, membrane-proximal external region POPC, 1-palmitoyl-2-oleoylphosphatidylcholine SLB, supported-lipid bilayers SPM, sphingomyelin |
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