Frazer Institute, Faculty of Medicine, University of Queensland, Brisbane, Queensland 4072, Australia.
Ian Frazer Centre for Children's Immunotherapy Research, Child Health Research Centre, Faculty of Medicine, University of Queensland, Brisbane, Queensland 4072, Australia.
Int Immunol. 2023 Dec 23;35(12):571-582. doi: 10.1093/intimm/dxad021.
Vaccination stands as the cornerstone in the battle against infectious diseases, and its efficacy hinges on several host-related factors like genetics, age, and metabolic status. Vulnerable populations, such as malnourished individuals, the obese, and the elderly, commonly exhibit diminished vaccine responses and efficacy. While the specific factors contributing to this impairment may vary, these individuals typically display a degree of metabolic dysregulation, thereby underscoring its potential significance as a fundamental determinant of suboptimal vaccine responses. 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 summarize the major metabolic pathways utilized 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.
疫苗接种是对抗传染病的基石，其效果取决于宿主相关的几个因素，如遗传、年龄和代谢状态。营养不良、肥胖和老年人等弱势群体通常表现出减弱的疫苗反应和效果。虽然导致这种损害的具体因素可能有所不同，但这些人通常表现出一定程度的代谢失调，因此强调了它作为影响疫苗反应不佳的基本决定因素的潜在意义。免疫代谢这一新兴领域旨在揭示免疫调节和代谢途径之间的复杂相互作用，最近的研究揭示了与各种疫苗反应和结果相关的不同代谢特征。在这篇综述中，我们总结了 B 和 T 细胞在疫苗反应过程中利用的主要代谢途径、它们复杂多样的代谢需求，以及微量营养素和代谢激素对疫苗结果的影响。此外，我们研究了全身代谢如何影响疫苗反应，以及代谢失调在弱势群体中可能导致疫苗反应减弱的证据。最后，我们反思了证明代谢失调对疫苗效果不佳的因果关系的挑战，并强调需要采用系统生物学方法，结合多模态分析和数学建模来揭示这些复杂相互作用的潜在机制。
