Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
mBio. 2024 Jan 16;15(1):e0303623. doi: 10.1128/mbio.03036-23. Epub 2023 Dec 19.
Antibodies represent the primary correlate of immunity following most clinically approved vaccines. However, their mechanisms of action vary from pathogen to pathogen, ranging from neutralization, to opsonophagocytosis, to cytotoxicity. Antibody functions are regulated both by antigen specificity (Fab domain) and by the interaction of their Fc domain with distinct types of Fc receptors (FcRs) present in immune cells. Increasing evidence highlights the critical nature of Fc:FcR interactions in controlling pathogen spread and limiting the disease state. Moreover, variation in Fc-receptor engagement during the course of infection has been demonstrated across a range of pathogens, and this can be further influenced by prior exposure(s)/immunizations, age, pregnancy, and underlying health conditions. Fc:FcR functional variation occurs at the level of antibody isotype and subclass selection as well as post-translational modification of antibodies that shape Fc:FcR-interactions. These factors collectively support a model whereby the immune system actively harnesses and directs Fc:FcR interactions to fight disease. By defining the precise humoral mechanisms that control infections, as well as understanding how these functions can be actively tuned, it may be possible to open new paths for improving existing or novel vaccines.
抗体是大多数经临床批准的疫苗接种后产生免疫的主要相关物。然而，它们的作用机制因病原体而异，包括中和、调理吞噬作用和细胞毒性。抗体的功能既受抗原特异性（Fab 结构域）的调节，也受其 Fc 结构域与免疫细胞中存在的不同类型 Fc 受体（FcR）相互作用的调节。越来越多的证据强调了 Fc: FcR 相互作用在控制病原体传播和限制疾病状态方面的关键性质。此外，在感染过程中 FcR 结合的变化已在一系列病原体中得到证实，并且这可以进一步受到先前暴露/免疫接种、年龄、妊娠和潜在健康状况的影响。Fc: FcR 功能的变化发生在抗体同种型和亚类选择以及抗体的翻译后修饰水平，这些修饰会影响 Fc: FcR 相互作用。这些因素共同支持了一种模型，即免疫系统积极利用和指导 Fc: FcR 相互作用来对抗疾病。通过确定控制感染的确切体液机制，以及了解如何主动调整这些功能，也许可以为改进现有或新型疫苗开辟新途径。
