Liposome-based vaccines for immune modulation: from antigen selection to nanoparticle design

Lozano Vigario, F. (2024)

Doctoral Thesis

Nanoparticles can be used as delivery systems for both small molecules and macromolecules such as proteins, peptides or oligonucleotides. This thesis focuses on the use of liposomes, nanometric vesicles formed by a lipid bilayer enclosing an aqueous core. Liposomes are highly versatile delivery systems. Fine tuning their physicochemical properties such as size, shape, rigidity or surface charge allows the control of the liposome's biological effect. Among the different applications for liposomes, antigen delivery is especially interesting. Liposomes can protect antigens from degradation, and they can direct the antigen delivery to specialised cells such as antigen-presenting cells (APCs), key for the induction of immune responses. APCs will present antigens to T cells to generate an immune response. The way in which these cells present the antigen will determine the type of immune response generated, either a pro-inflammatory response necessary to fight viral and bacterial infections or a tolerogenic response useful to temper down inflammation, for example in the context of cardiovascular diseases like atherosclerosis. Therefore, these formulations can be used as vaccines against inflammatory diseases and as prophylactic vaccines against infectious diseases. In this thesis, we examine key aspects of liposome formulations including the elucidation of target antigens to be used in a tolerogenic vaccine against atherosclerosis, the manufacture of these formulations using microfluidics, the use of vitaminD3 as a tolerogenic adjuvant and the role of liposome rigidity in the tolerogenic effect of these nanoparticles. Furthermore, we explore the use of liposomes to induce protective anti-viral immunity against influenza.

• Nanoparticles
• Liposomes
• Atherosclerosis
• Tolerance
• Immune modulation
• Influenza
• Microfluidics
• Immunopeptidomics

• All authors: Lozano Vigario, F.
• Supervisor: Bouwstra, J.A.; Kros, A.; Slütter, B.A.
• Committee: Irth, H.; Lange, E.C.M. de; Raemdonck, K.; Mastrobattista, E.; Gistera, A.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University
• Date: 2024-09-10
• Sponsorship: The research was financially supported by Health Holland and Samen Werkende Gezondheidsfondsen (SGF)