Modulating Antigen Availability in Lymphoid Organs to Shape the Humoral Immune Response to Vaccines

Primary immune responses following vaccination are initiated in draining lymph nodes, where naive T and B cells encounter Ag and undergo coordinated steps of activation. For humoral immunity, the amount of Ag present over time, its localization to follicles and follicular dendritic cells, and the Ag's structural state all play important roles in determining the subsequent immune response. Recent studies have shown that multiple elements of vaccine design can impact Ag availability in lymphoid tissues, including the choice of adjuvant, physical form of the immunogen, and dosing kinetics. These vaccine design elements affect the transport of Ag to lymph nodes, Ag's localization in the tissue, the duration of Ag availability, and the structural integrity of the Ag. In this review, we discuss these findings and their implications for engineering more effective vaccines, particularly for difficult to neutralize pathogens. The Journal of Immunology, 2024, 212: 171-178.