Materials engineering allows the precise design of spatio-temporal cell‒vaccine interactions. This sequence of events is based on complex spatial and temporal control of each step, which needs to be dissected and modulated to control the immune response by vaccination (Fig. The long-term memory response remains for months to years following vaccination, providing protection against future infection. Activation of the innate immune system and migration of key cells and vaccine components to lymph nodes occurs within hours, followed by B cell and T cell maturation within days and weeks. After the immune response is mounted, the blood enables antibodies and memory T cells to reach infected tissue and protect the entire body. The blood provides an important route for innate immune cells to quickly infiltrate the site of vaccination or infection in the early immune response. Lymph nodes downstream of the location of pathogen or vaccine exposure are called draining lymph nodes, and are key sites from the beginning of the immune response throughout the development of mature effector B cells and T cells. Tissues at the interface with the outside world (for example, skin, lungs and mucosal sites) are the primary locations of infections, and therefore contain tissue-resident immune cells and are constantly patrolled by migratory immune cells. This coordinated action of immune cells requires precise spatial and temporal cues. The vaccine immune response occurs in multiple locations - peripheral tissues, lymph nodes and systemic circulation - each of which has its own cell composition and function. The immune response to infection or vaccination depends on the complex coordination between cells across the body. HBV, hepatitis B virus MPL, monophosphoryl lipid A siRNA, small interfering RNA TLR, Toll-like receptor. Memory T cells also use the circulatory system to inspect the body for foreign invaders. Following vaccination, plasma cells secrete antigen-specific antibodies, which travel through the circulatory system to tissues, where they respond immediately upon pathogen exposure. These signals are crucial in triggering cell infiltration to the injection site. d | Immediately following vaccine administration, local innate cells release cytokines into the circulation to enable a coordinated response. As the immune response develops, sites of B cell development, called germinal centres, form in the B cell zones of the lymph nodes. Early in the vaccine response, lymph node-resident phagocytic cells and migratory innate cells arriving from peripheral tissues present antigen and produce inflammatory signals to activate T cells. c | Maturation and development of a potent adaptive response continues in lymph nodes downstream of the vaccination site (draining lymph nodes). Soluble vaccine components and activated cells enter the lymphatics and travel to local lymph nodes. As innate immune cells become activated, they release cytokines that attract other immune cells from the bloodstream to the site of administration. The antigen component of the vaccine is endocytosed and broken down by APCs before being presented on the APC surface major histocompatibility complex (MHC) molecules. At the site of administration, innate immune cells, such as neutrophils and antigen-presenting cells (APCs), first encounter the antigen and adjuvant. b | Following administration of a vaccine, interactions between cells and vaccine components lead to a strong and lasting response. In this Review, we highlight the biological mechanisms underlying strong humoral and cell-mediated immune responses and explore materials design strategies to manipulate and control these mechanisms.Ī | Timeline of major events in drug delivery and vaccine development. Materials-based vaccination strategies can augment the immune response by improving innate immune cell activation, creating local inflammatory niches, targeting lymph node delivery and controlling the time frame of vaccine delivery, with the goal of inducing enhanced memory immunity to protect against future infections. Material platforms, such as nanoparticles, hydrogels and microneedles, can be engineered to spatially and temporally control the interactions of vaccine components with immune cells. As our knowledge of the immune system deepens, it becomes clear that vaccine components must be in the right place at the right time to orchestrate a potent and durable response. However, increasing the potency, quality and durability of the vaccine response remains a challenge. Vaccines are the key technology to combat existing and emerging infectious diseases.
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