Immunological perspectives on spatial and temporal vaccine delivery

The so-called rational design of vaccines has been a very attractive concept and also an important direction for vaccine research and development. However, the underlying rationales, especially on the immunological aspect, remain less systemically and deeply understood. Given the critical role of lymph nodes (LNs) in the induction of B and T cell responses upon vaccination, LN targeting has been a popular strategy in vaccine design. The LN is a highly organized structure; induction of adaptive immune response is highly orchestrated by various types of LN stromal cells and hematopoietic immune cells both spatially and temporally. Thus, not only LN targeting, but also cellular targeting and even subcellular compartment targeting should be considered for specifically enhanced vaccine efficacy. Moreover, temporal control of vaccine antigen and adjuvant delivery may also optimize the immune response.