Chapter 2 - How Vaccines Work

Abstract

Vaccine responses depend upon their interactions with the immune system. This chapter aims to give a simplified vision of these interactions. The goal is to provide the immunological bases that should guide vaccine design and vaccination strategies. Early inflammatory events that follow vaccine administration take place at the injection site and are essential in determining the outcome of vaccination. Thus vaccine formulations may influence the initial activation pattern of dendritic cells that can capture vaccine antigens, migrate to the draining lymph nodes (dLNs), and present vaccine peptides to specific T cells. Free antigen can also diffuse to the dLNs, be captured by subcapsular macrophages, and translocated to the B-cell zone. Vaccine characteristics have a significant impact on this process and on the generation of extrafollicular responses and germinal centers, which play a major role in the outcome of humoral responses. A critical aspect of vaccine efficacy is the duration of protection. In most cases, it depends on antibody persistence and the quality of memory induced by priming doses. Both B- and T-cell memory are slowly maturing and this allows sufficient delay before boosting. Responses to live viral vaccines are more disseminated and the exposure to vaccine antigens is often prolonged. This may greatly influence the establishment and duration of immunological memory. The understanding of the T- and B-cell machinery should help to define optimal pathways toward protective vaccine responses.