Chapter 5: Nanoparticles, Immunomodulation and Vaccine Delivery

Interest in nanoparticles and their use as vaccine carriers and adjuvants has greatly increased in recent times. However, despite current intense research in this field, the ways in which the immune system responds to nanoscale particulates are still being defined. This chapter will review the physical and chemical characteristics of nanoparticles 1–1000 nm in diameter, considering size, shape, surface charge and chemistry, and their effects on the immune system, including drainage to the lymph nodes (LNs), uptake by antigen-presenting cells (APCs) and the triggering of intracellular signalling pathways. We examine how particle size affects nanoparticle uptake by the key innate stimulators of the immune system, i.e., dendritic cells (DCs), and how nanoparticles modulate DCs and the induction of multiple arms of the immune response, including antibody production and CD4 and CD8 T cell responses via conventional and cross-priming pathways. We further discuss how inert nanoparticles, which by themselves may not necessarily promote the significant inflammation usually associated with adjuvants, can nevertheless induce powerful immunity, suggesting nanotechnology has outstanding potential to deliver safe synthetic vaccines against today's major diseases such as cancer and malaria. Biodegradable or biocompatible nanoparticles, such as polymeric particles, chitosan, polystyrene, gold/silver particles and magnetic/metallic particles, are discussed in relation to the induction of immune responses and vaccine formulations. An in-depth understanding of how nanoparticles physicochemically modulate the immune system supports the rational development of nanoparticle-based vaccines, as well as safe nanoparticulate drug delivery systems.