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

Damm D, Suleiman E, Theobald H, Wagner J, Batzoni M, Kohlhauser BAN, Walkenfort B, Albrecht JC, Ingale J, Yang L, Hasenberg M, Wyatt RT, Vorauer-Uhl K, Überla K, Temchura V (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 14

Article Number: 1385

Journal Issue: 7

DOI: 10.3390/pharmaceutics14071385

Abstract

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.

Authors with CRIS profile

Involved external institutions

Universität für Bodenkultur Wien (BOKU) / University of Natural Resources and Life Sciences, Vienna Austria (AT) Universitätsklinikum Essen Germany (DE) Scripps Research Institute (TSRI) United States (USA) (US) Takeda Pharmaceuticals U.S.A., Inc. United States (USA) (US)

How to cite

APA:

Damm, D., Suleiman, E., Theobald, H., Wagner, J., Batzoni, M., Kohlhauser, B.A.N.,... Temchura, V. (2022). Design and Functional Characterization of HIV-1 Envelope Protein-Coupled T Helper Liposomes. Pharmaceutics, 14(7). https://doi.org/10.3390/pharmaceutics14071385

MLA:

Damm, Dominik, et al. "Design and Functional Characterization of HIV-1 Envelope Protein-Coupled T Helper Liposomes." Pharmaceutics 14.7 (2022).

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