Mannosylated Liposomes with Built-in Peptidoglycan Based Immunomodulators for Subunit Vaccine Formulations

Abstract

The aim of the present study is preparation of mannosylated liposomes with built-in small molecule immunopotentiators for targeted, receptors mediated, delivery of antigens. The liposomes were mannosylated in two ways, by covalent attachment of p-aminophenyl-α-Dmannopyranoside to the preformed liposomes and by incorporation of synthetic mono-, di-and tetramannosyl-lipoconjugates into the lipid bilayer of liposomes. Four different mannosylated liposome formulations with incorporated model antigen, ovalbumin (OVA), and immunomodulators, PGM and Ad2TP2, were prepared and characterized. The influence of mannosylated liposome formulations on the antigen-specific humoral immune response was investigated. It has been shown that mannosylated liposomal formulations did not enhance the humoral immune response and production of anti-OVA antibodies but they significantly affected the type of OVA specific immune reaction and directed it towards Th1 type.

Structural Fine-Tuning of Desmuramylpeptide NOD2 Agonists Defines Their In Vivo Adjuvant Activity

“…Namely, the negatively charged liposomes showed diminished IgG1 activity. Mannosylated liposomes, on the other hand, enhanced the production of IgG2a antibodies, which is in agreement with previous reports of Th1-biased immune responses upon immunization with mannosylated liposomes with NOD2 agonist adjuvant . (iv) Finally, regardless of the liposomal composition, 75 increased the levels of IgG antibodies compared to the controls without adjuvant, with comparable or stronger adjuvant activities than MDP.…”

“…Mannosylated liposomes, on the other hand, enhanced the production of IgG2a antibodies, which is in agreement with previous reports of Th1-biased immune responses upon immunization with mannosylated liposomes with NOD2 agonist adjuvant. 125 (iv) Finally, regardless of the liposomal composition, 75 increased the levels of IgG antibodies compared to the controls without adjuvant, with comparable or stronger adjuvant activities than MDP. Additionally, while MDP elicited a predominantly Th2-biased IgG1 response, 75 also augmented the production of ovalbumin-specific IgG2a antibodies, resulting in a mixed Th1/Th2 response.…”

Lipidation of NOD2 Agonists with Adamantane and Stearoyl Moieties Differentially Regulates Their In Vivo Adjuvant Activity

“…Next-generation adjuvants typically include rationally designed synthetic immune potentiators that are appropriately formulated [9][10][11]. Liposomes with built-in immunostimulants represent potent adjuvant formulations that act as a depot at the injection site, ensure the protection of antigens from the action of the hydrolytic enzymes, and, most importantly, enhance the production of specific cytokines and strengthen the overall immune response [12,13]. Liposomes' size, surface charge, and composition can greatly affect the efficiency of liposomes as drug delivery systems [14][15][16].…”

“…Finally, they were evaluated for their adjuvant potential in a well-defined mouse model in conjunction with a model antigen ovalbumin. strengthen the overall immune response [12,13]. Liposomes' size, surface charge, and composition can greatly affect the efficiency of liposomes as drug delivery systems [14][15][16].…”