Modulation of immune responses to liposomal vaccines by intrastructural help

Damm D, Suleiman E, Wagner J, Klessing S, Pfister F, Elsayed H, Walkenfort B, Stobrawe J, Mayer J, Lehner E, Müller-Schmucker S, Hasenberg M, Wyatt RT, Vorauer-Uhl K, Temchura V, Überla K (2023)

Publication Type: Journal article

Publication year: 2023

Journal

European Journal of Pharmaceutics and Biopharmaceutics Elsevier

Book Volume: 192

Pages Range: 112-125

DOI: 10.1016/j.ejpb.2023.10.003

Abstract

The encapsulation of HIV-unrelated T helper peptides into liposomal vaccines presenting trimers of the HIV-1 envelope glycoprotein (Env) on the surface (T helper liposomes) may recruit heterologous T cells to provide help for Env-specific B cells. This mechanism called intrastructural help can modulate the HIV-specific humoral immune response. In this study, we used cationic T helper liposomes to induce intrastructural help effects in a small animal model. The liposomes were functionalized with Env trimers by a tag-free approach designed to enable a simplified GMP production. The pre-fusion conformation of the conjugated Env trimers was verified by immunogold electron microscopy (EM) imaging and flow cytometry. The liposomes induced strong activation of Env-specific B cells in vitro. In comparison to previously established anionic liposomes, cationic T helper liposomes were superior in CD4+ T cell activation after uptake by dendritic cells. Moreover, the T helper liposomes were able to target Env-specific B cells in secondary lymphoid organs after intramuscular injection. We also observed efficient T helper cell activation and proliferation in co-cultures with Env-specific B cells in the presence of cationic T helper liposomes. Mouse immunization experiments with cationic T helper liposomes further revealed a modulation of the Env-specific IgG subtype distribution and enhancement of the longevity of antibody responses by ovalbumin- and Hepatitis B (HBV)-specific T cell help. Thus, clinical evaluation of the concept of intrastructural help seems warranted.

Authors with CRIS profile

Dominik Damm Institute of Clinical and Molecular Virology Jannik Wagner Institute of Clinical and Molecular Virology Felix Pfister Department of Otorhinolaryngology – Head and Neck Surgery Jule Stobrawe Lehrstuhl für Klinische und Molekulare Virologie Sandra Müller-Schmucker Institute of Clinical and Molecular Virology Vladimir Temchura Institute of Clinical and Molecular Virology Klaus Überla Lehrstuhl für Klinische und Molekulare Virologie

Involved external institutions

Universität für Bodenkultur Wien (BOKU) / University of Natural Resources and Life Sciences, Vienna AT Austria (AT) Polymun Scientific Immunbiologische Forschung GmbH AT Austria (AT) National Research Centre (NRC) / المركز القومي للبحوث EG Egypt (EG) Scripps Research Institute (TSRI) US United States (USA) (US) Universitätsklinikum Essen DE Germany (DE)

How to cite

APA:

Damm, D., Suleiman, E., Wagner, J., Klessing, S., Pfister, F., Elsayed, H.,... Überla, K. (2023). Modulation of immune responses to liposomal vaccines by intrastructural help. European Journal of Pharmaceutics and Biopharmaceutics, 192, 112-125. https://doi.org/10.1016/j.ejpb.2023.10.003

MLA:

Damm, Dominik, et al. "Modulation of immune responses to liposomal vaccines by intrastructural help." European Journal of Pharmaceutics and Biopharmaceutics 192 (2023): 112-125.

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