Systemic immunometabolism and responses to vaccines: insights from T and B cell perspectives.

Vaccination stands as the cornerstone in the battle against infectious diseases, and its efficacy hinges upon multifaceted host-related factors encompassing genetics, age, and metabolic status. Remarkably, suboptimal immune responses triggered by metabolic dysregulation is frequently observed in susceptible populations - ranging from malnourished individuals to the obese and elderly - pose a formidable threat to vaccine efficacy. The emerging field of immunometabolism aims to unravel the intricate interplay between immune regulation and metabolic pathways, and recent research has revealed diverse metabolic signatures linked to various vaccine responses and outcomes. In this review, we summarise the major metabolic pathways utilised by B and T cells during vaccine responses, their complex and varied metabolic requirements, and the impact of micronutrients and metabolic hormones on vaccine outcomes. Furthermore, we examine how systemic metabolism influences vaccine responses and the evidence suggesting that metabolic dysregulation in vulnerable populations can lead to impaired vaccine responses. Lastly, we reflect on the challenge of proving causality with respect to the contribution of metabolic dysregulation to poor vaccine outcomes, and highlight the need for a systems biology approach that combines multimodal profiling and mathematical modelling to reveal the underlying mechanisms of such complex interactions.