Circadian rhythmicity and vaccination

Evidence from in vitro, ex vivo, and in vivo studies indicates that several immune cell functions are dependent on circadian rhythmicity, including cell adhesion, migration and homing, cell-cell interaction, cytokine production, cell cytotoxicity, phagocytosis, and bactericidal activity, amongst others. Likewise, ex vivo experiments have shown that the percentages of blood leukocyte subpopulations vary along the day. The effect of time on the day in the quality of an immune response is perhaps more evident in the lethal effect of lipopolysaccharides (LPS) in a model of endotoxic shock; mice that have been administered LPS at night are more likely to die than those treated in the morning with the same dose of LPS. Circadian-based differences in the immune responses have been attributed in part to metabolic differences occurring along the day. Current knowledge suggests that vaccine effectivity is dependent on the time of the day at which vaccination is applied. However, studies designed to explore this possibility are still sparse and controversial. This chapter critically evaluates current literature on the topic while it outlines some basic principles, and key research questions that require to be addressed in the near future if the time of the day of vaccination is meant to allow for the design of better vaccination procedures.