Figure 1. Mechanisms by which nanoparticles alter the induction of immune responses. The immunostimulatory activity of nanocarriers such as liposomes, archaeosomes and virosomes depends on

diverse mechanisms: antigen delivery, particle size-dependent tissue penetration … Adjuvants The ability R428 dissolve solubility to enhance the immune response of vaccines by certain compounds was first demonstrated with aluminum salts, termed ‘adjuvants’, added to killed or attenuated pathogens. Their functions were related to the ability to form a depot which prolonged antigen exposure to APCs. However, efficient adjuvants also stimulate the immune system by direct interaction with APCs. The nature of immune adjuvants is large and heterogeneous. Adjuvants are divided into immunostimulants and delivery systems. Immunostimulants interact with specific receptors, like TLRs and others, while delivery systems increase the immune response by multiple mechanisms, depending on their particular characteristics [Leroux-Roels, 2010; Alving et al. 2012]. Thus, modern vaccines comprise adjuvants such as pathogen-derived subcellular components, recombinant proteins, peptides and nucleic acid sequences [Zepp, 2010; Perez et al. 2013; Reed et al. 2013]. In addition, due to better knowledge of the immune system and improvements in formulation technology, effective therapeutic cancer vaccines are developed [Joshi et al. 2012]. Today’s challenges in vaccine development

are linked to complex pathogens [e.g. malaria,

tuberculosis, human immunodeficiency virus (HIV)] and to antigens susceptible to genetic mutations (e.g. influenza) as well as to subjects with a compromised or dysfunctional immune system [Leroux-Roels, 2010]. Nanoparticulate carriers provide adjuvant activity by enhancing antigen delivery or by activating innate immune responses. Strength and mechanisms of immunostimulation induced by nanocarrier vaccines depend on various factors, such as chemical composition, particle size and homogeneity, charge, nature and location of antigens and/or adjuvants within the carrier and, last but not least, the site of administration (see Figure 2) [Watson et al. 2012; Brito et al. 2013; Gregory et al. 2013; Smith et al. 2013; Zaman et al. 2013]. Figure 2. Schematic representation of a small unilamellar liposome showing the versatility of incorporation of various compounds either by encapsulation in the aqueous Cilengitide inner space or by integration in the bilayer or surface attachment on the lipid bilayer membrane. … Liposomes: ideal carriers for antigens and adjuvants The ability of liposomes to induce immune responses to incorporated or associated antigens was first reported by Gregoriadis and Allison [Allison and Gregoriadis, 1974, 1976]. Since then, liposomes and liposome-derived nanovesicles such as archaeosomes and virosomes have become important carrier systems and the interest for liposome-based vaccines has markedly increased.