Design and Functional Characterization of HIV-1 Envelope Protein-Coupled T Helper Liposomes.

Autor: Damm D; Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany., Suleiman E; Department of Biotechnology, University of Natural Resources and Life Sciences, 1190 Vienna, Austria., Theobald H; Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany., Wagner JT; Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany., Batzoni M; Department of Biotechnology, University of Natural Resources and Life Sciences, 1190 Vienna, Austria., Ahlfeld Née Kohlhauser B; Department of Biotechnology, University of Natural Resources and Life Sciences, 1190 Vienna, Austria., Walkenfort B; Electron Microscopy Unit (EMU), Imaging Center Essen (IMCES), Faculty of Medicine, University of Duisburg-Essen, 45147 Essen, Germany., Albrecht JC; Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany., Ingale J; Vaccine Business Unit, Takeda Pharmaceuticals, Cambridge, MA 02139, USA., Yang L; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Hasenberg M; Electron Microscopy Unit (EMU), Imaging Center Essen (IMCES), Faculty of Medicine, University of Duisburg-Essen, 45147 Essen, Germany., Wyatt RT; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Vorauer-Uhl K; Department of Biotechnology, University of Natural Resources and Life Sciences, 1190 Vienna, Austria., Überla K; Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany., Temchura V; Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2022 Jun 30; Vol. 14 (7). Date of Electronic Publication: 2022 Jun 30.
DOI: 10.3390/pharmaceutics14071385
Abstrakt: Functionalization of experimental HIV-1 virus-like particle vaccines with heterologous T helper epitopes (T helper VLPs) can modulate the humoral immune response via intrastructural help (ISH). Current advances in the conjugation of native-like HIV-1 envelope trimers (Env) onto liposomes and encapsulation of peptide epitopes into these nanoparticles renders this GMP-scalable liposomal platform a feasible alternative to VLP-based vaccines. In this study, we designed and analyzed customizable Env-conjugated T helper liposomes. First, we passively encapsulated T helper peptides into a well-characterized liposome formulation displaying a dense array of Env trimers on the surface. We confirmed the closed pre-fusion state of the coupled Env trimers by immunogold staining with conformation-specific antibodies. These peptide-loaded Env-liposome conjugates efficiently activated Env-specific B cells, which further induced proliferation of CD4+ T cells by presentation of liposome-derived peptides on MHC-II molecules. The peptide encapsulation process was then quantitatively improved by an electrostatically driven approach using an overall anionic lipid formulation. We demonstrated that peptides delivered by liposomes were presented by DCs in secondary lymphoid organs after intramuscular immunization of mice. UFO (uncleaved prefusion optimized) Env trimers were covalently coupled to peptide-loaded anionic liposomes by His-tag/NTA(Ni) interactions and EDC/Sulfo-NHS crosslinking. EM imaging revealed a moderately dense array of well-folded Env trimers on the liposomal surface. The conformation was verified by liposomal surface FACS. Furthermore, anionic Env-coupled T helper liposomes effectively induced Env-specific B cell activation and proliferation in a comparable range to T helper VLPs. Taken together, we demonstrated that T helper VLPs can be substituted with customizable and GMP-scalable liposomal nanoparticles as a perspective for future preclinical and clinical HIV vaccine applications. The functional nanoparticle characterization assays shown in this study can be applied to other systems of synthetic nanoparticles delivering antigens derived from various pathogens.
Databáze: MEDLINE
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