Modulation of immune responses to liposomal vaccines by intrastructural help

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 192; pp. 112 - 125
• Main Authors: Damm, Dominik, Suleiman, Ehsan, Wagner, Jannik T., Klessing, Stephan, Pfister, Felix, Elsayed, Hassan, Walkenfort, Bernd, Stobrawe, Jule, Mayer, Julia, Lehner, Elisabeth, Müller-Schmucker, Sandra M., Hasenberg, Mike, Wyatt, Richard T., Vorauer-Uhl, Karola, Temchura, Vladimir, Überla, Klaus
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2023
• Subjects: Animals; env Gene Products, Human Immunodeficiency Virus - chemistry; Env trimer; Functionalization; HIV Antibodies; HIV Infections; HIV vaccine; HIV-1; IgG subtype; Immunity, Humoral; Intrastructural help; Liposomes - chemistry; Mice; Nanoparticle; Peptide encapsulation; T helper liposomes; Vaccines; IgG subtype; Peptide encapsulation; Functionalization; Nanoparticle; HIV vaccine; Intrastructural help; Env trimer; T helper liposomes
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2023.10.003

[Display omitted] 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.