Controlling timing and location in vaccines

Summary

Vaccines are one of the most powerful technologies supporting public health. The adaptive immune response induced by immunization arises following appropriate activation and differentiation of T and B cells in lymph nodes.

Among many parameters impacting the resulting immune response, the presence of antigen and inflammatory cues for an appropriate temporal duration within the lymph nodes, and further within appropriate subcompartments of the lymph nodes– the right timing and location– play a critical role in shaping cellular and humoral immunity. Here we review recent advances in our understanding of how vaccine kinetics and biodistribution impact adaptive immunity, and the underlying immunological mechanisms that govern these responses.

We discuss emerging approaches to engineer these properties for future vaccines, with a focus on subunit vaccines.

Highlights

• Vaccines are one of the oldest tools for promoting public health, but their importance has only grown as we face newly-arising pathogens.
• Technologies addressing the issues of timing and localization will be critical for achieving the goals of such vaccine development programs.
• Pathogens that establish chronic infections and/or evade immunity will necessitate optimization of vaccine targeting and timing.
• Antigen availability plays a deterministic role in the strength and type of B cell and T cell responses induced by immunization.
• As we seek vaccines capable of driving more diverse and robust humoral immune responses or more effectively establish protective T cell responses, adjuvants play an increasingly important role.
• The need for high levels of safety at low cost remain critical issues that will ultimately govern what approaches can move forward in the clinic vs. those that remain preclinical proofs of concept.