Liposomes as vaccine delivery systems: a review of the recent advances

Abstract

Liposomes and liposome-derived nanovesicles such as archaeosomes and virosomes have become important carrier systems in vaccine development and the interest for liposome-based vaccines has markedly increased. A key advantage of liposomes, archaeosomes and virosomes in general, and liposome-based vaccine delivery systems in particular, is their versatility and plasticity. Liposome composition and preparation can be chosen to achieve desired features such as selection of lipid, charge, size, size distribution, entrapment and location of antigens or adjuvants. Depending on the chemical properties, water-soluble antigens (proteins, peptides, nucleic acids, carbohydrates, haptens) are entrapped within the aqueous inner space of liposomes, whereas lipophilic compounds (lipopeptides, antigens, adjuvants, linker molecules) are intercalated into the lipid bilayer and antigens or adjuvants can be attached to the liposome surface either by adsorption or stable chemical linking. Coformulations containing different types of antigens or adjuvants can be combined with the parameters mentioned to tailor liposomal vaccines for individual applications. Special emphasis is given in this review to cationic adjuvant liposome vaccine formulations. Examples of vaccines made with CAF01, an adjuvant composed of the synthetic immune-stimulating mycobacterial cordfactor glycolipid trehalose dibehenate as immunomodulator and the cationic membrane forming molecule dimethyl dioctadecylammonium are presented. Other vaccines such as cationic liposome-DNA complexes (CLDCs) and other adjuvants like muramyl dipeptide, monophosphoryl lipid A and listeriolysin O are mentioned as well. The field of liposomes and liposome-based vaccines is vast. Therefore, this review concentrates on recent and relevant studies emphasizing current reports dealing with the most studied antigens and adjuvants, and pertinent examples of vaccines. Studies on liposome-based veterinary vaccines and experimental therapeutic cancer vaccines are also summarized.

Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies

“…Lung deposition and retention can be targeted via modifications of the physicochemical characters such as size, charge, and formulation composition ratio and lipid type. Liposomes have been used as carriers for vaccines [58], nucleic acids such as siRNA, miRNA, lncRNA, DNA for respiratory conditions such as COPD, CF, and lung cancer. Although some of these applications are commonly administered via invasive routes, a number of cell and animal studies have proved their suitability for local lung delivery [56,59,60].…”

Liposomal systems as carriers for bioactive compounds

“…However, their cell-like structure led to investigations on their efficacy as a tool to carry potent molecules into the human body. Nowadays they are used for the encapsulation of unstable compounds considered to be essential to human health, such as antioxidants, antimicrobials, bioactive elements, antigenic proteins, thereby preserving their functionality (Madni et al 2014;Schwendener 2014;Patil and Jadhav 2014). Liposomal vesicles have emerged as one of the novel carrier systems most studied by the scientific community over the past decades and have revolutionized research in many different fields, such as cosmetics, drugs, food, agriculture, with applications in chemotherapy treatments, gene therapy, vaccines, antimicrobial agents, among others (Madni et al 2014).…”

“…Depending on the chemical properties of the liposome, hydrophilic compounds (proteins, peptides, nucleic acids, carbohydrates) can be entrapped within the aqueous core, thereby increasing penetration of these compounds through physiological lipophilic membranes, whereas lipophilic compounds (linker molecules, antigens, adjuvants, lipopeptides) can be intercalated inside the lipid bilayer, thereby increasing their solubility in the aqueous body fluids (Fig. 1) (Rahman et al 1974;Schwendener 2014).…”

“…Antigens or adjuvants can be attached to the liposome surface either by adsorption or stable chemical linking (Torchilin 2005;Watson et al 2012). Coformulations containing different types of adjuvants or antigens can be combined with specific liposome properties for the development of liposomal vaccines for individual applications (Schwendener 2014). Liposomes provide antigens or adjuvants with greater protection from external degradation caused by enzymes (Chaize et al 2004), and because they are prepared from natural materials or their synthetic derivatives, they are biocompatible and biodegradable (Rooijen and Nieuwmegen 1980).…”

“…Together with the ability to induce strong immune responses provided by co-formulated adjuvants, liposome-based vaccines provide the fundamental properties required for the development of modern vaccine formulations (Schwendener 2014).…”