Moysi Eirini, Paris Robert M, Le Grand Roger, Koup Richard A, Petrovas Constantinos
Tissue Analysis Core, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA.
Translational Medicine, Infectious Diseases, Moderna, Cambridge, MA, USA.
Expert Rev Vaccines. 2022 May;21(5):633-644. doi: 10.1080/14760584.2022.2045198. Epub 2022 Mar 9.
During the last century, changes in hygiene, sanitation, and the advent of childhood vaccination have resulted in profound reductions in mortality from infectious diseases. Despite this success, infectious diseases remain an enigmatic public health threat, where effective vaccines for influenza, human immunodeficiency virus (HIV), tuberculosis, and malaria, among others remain elusive.
In addition to the immune evasion tactics employed by complex pathogens, our understanding of immunopathogenesis and the development of effective vaccines is also complexified by the inherent variability of human immune responses. Lymph nodes (LNs) are the anatomical sites where B cell responses develop. An important, but understudied component of immune response complexity is variation in LN immune dynamics and in particular variation in germinal center follicular helper T cells (Tfh) and B cells which can be impacted by genetic variation, aging, the microbiome and chronic infection.
We describe the contribution of genetic variation, aging, microbiome and chronic infection on LN immune dynamics and associated Tfh responses and offers perspective on how inclusion of LN immune subset and cytoarchitecture analyses, along with peripheral blood biomarkers can supplement systems vaccinology or immunology approaches for the development of vaccines or other interventions to prevent infectious diseases.
在上个世纪,卫生条件、环境卫生的改善以及儿童疫苗接种的出现,使得传染病死亡率大幅下降。尽管取得了这一成功,但传染病仍然是一个神秘的公共卫生威胁,例如针对流感、人类免疫缺陷病毒(HIV)、结核病和疟疾等的有效疫苗仍然难以实现。
除了复杂病原体采用的免疫逃避策略外,人类免疫反应的固有变异性也使我们对免疫发病机制和有效疫苗开发的理解变得复杂。淋巴结(LNs)是B细胞反应发生的解剖部位。免疫反应复杂性的一个重要但研究不足的组成部分是淋巴结免疫动力学的变化,特别是生发中心滤泡辅助性T细胞(Tfh)和B细胞的变化,这些变化可能受到基因变异、衰老、微生物群和慢性感染的影响。
我们描述了基因变异、衰老、微生物群和慢性感染对淋巴结免疫动力学及相关Tfh反应的影响,并就如何将淋巴结免疫亚群和细胞结构分析与外周血生物标志物相结合,以补充系统疫苗学或免疫学方法,用于开发预防传染病的疫苗或其他干预措施提供了观点。