Cationic Nanostructures for Vaccines

Cationic lipid bilayers, particles, polysaccharides and a variety of hybrid nanostructures provide adequate matrixes for supporting antigens such as peptides, proteins, DNA or oligonucleotides on model surfaces (latex, silica, silicon wafers, self-assembled monolayers, metals, polymers, insoluble drugs, biological cells and viruses).Particulate vaccines are currently an area receiving a high level of attention [1-3]. Particles deliver both antigen and adjuvant into the same population of antigen presenting cells limiting both the systemic distribution of the adjuvant and its potential toxicity [1]. Biological particlesrepresented by live or attenuated bacterial vacines, engineered biological vectors and virus-like particles are often less safe than synthetic particulates for which quality control and validation in vaccine development and production are more rapid [2]. While developing novel particulate vaccines, particle size and charge do matter [2]. Virus-sized particles (20–200 nm) are usually taken up by endocytosis via clathrin-coated vesicles, caveolae or their independent receptors [4], and preferentially ingested by dendritic cells (DC). Larger sized particles such as bacteria (500– 5000 nm) are predominantly taken up by phagocytosis, and primarily ingested by macro‐ phages. All particles used in vaccine formulations are consequently internalized efficiently by antigen presenting cells by one or a combination of the quoted mechanisms [5, 6]. Particles with diameters smaller than 500 nm, in particular the nanometric ones with sizes in the 40– 100 nm range are more eficient to promote CD8 and CD4 type 1 T cell responses than those with diameters above 500 nm, although the latter could induce good type 2 and antibody responses [5]. Cationic microparticles are effectively taken up both by macrophages and dendritic cells since electrostatic attraction promotes particle binding and subsequent inter‐ nalization. Cationized polymeric particles carrying antigen significantly enhanced both antibody production and cytotoxic T cells at low antigen dose [7] and induced maturation of dendritic cells [8, 9]. As a consequence particles for vaccines should be positive and available over a range of sizes. Cationic particles of aluminium compounds, identified as having