From Antigen Delivery System to Adjuvanticy: The Board Application of Nanoparticles in Vaccinology

Abstract

In the last years, nanotechnologies have raised great interest because of the potential applications of engineered nanoparticles in nanomedicine (i.e., in vaccination, in diagnostic imaging procedures, and as therapeutic drug delivery systems). The use of nanoparticles in medicine has brought about the issue of their interaction with the immune system for two main reasons: first, understanding how long nanomedicines could persist in the organism and exert their beneficial effects before being recognized and eliminated by our defensive systems; second, understanding how the immune responses can be modulated by nanoparticles in order to obtain optimal effects. This issue is crucial in vaccine formulations based on the use of nanoparticles, which can operate both as a delivery system to enhance antigen processing and as an immunostimulatory adjuvant to induce and amplify protective immunity, in part because of their ability to activate the inflammasome and induce the maturation of interleukin 1β. Nanoparticles can be excellent adjuvants due to their biocompatibility and their physicochemical properties (e.g., size, shape, and surface charge), which can be tailored to obtain different immunological effects. This review provides an overview of recent strategies for the use of nanoparticles as promising/attractive adjuvants for novel prophylactic and therapeutic vaccines. The use of nanovaccines, with their practically infinite possibilities of specific design, could open the way to precision vaccinology, i.e., vaccine formulations tailored on the individual immune reactivity status.

Keywords: adjuvants; inflammation; nanoparticles; vaccines.

Figure 1

The NLRP3 activation and the production of IL-1β. A first stimulus, typically TLR agonists such as bacterial LPS (upper right), starts the activation by upregulating the expression of the genes encoding IL-1β and caspase-1, which are synthesized as inactive precursors (pro-caspase-1 and pro-IL-1β). The inflammasome is activated by a second type of stimuli (upper left), occurring intracellularly and being either endogenous or exogenous (particles and crystals of various origin, microorganisms, and reactive oxygen species), collectively dubbed danger-associated molecular patterns (DAMPs). These are able to change the inactive conformation of NLRP3, thus allowing the complexing of a number of NLRP3 molecules, an event facilitated by cathepsin B (released from ruptured lysosomes). The inflammasome assembles with the recruitment of adaptor proteins (in this case ASC), which in turn can take in the pro-caspase-1 and induce its cleavage and activation. Active caspase-1 then cleaves and helps the secretion of mature active IL-1β.