抗体可结晶片段效应功能及其在疫苗免疫学检测中的应用进展

Progress in crystallizable fragment effector functions and its application in the evaluation of vaccines

摘要:

抗体是疫苗发挥保护作用的核心效应分子。传统观点认为抗体主要通过中和作用实现保护，即抗体的抗原结合片段(antigen-binding fragment, Fab)结构域能够阻断病毒与宿主细胞表面受体结合，从而抑制感染。近年来研究发现，抗体的可结晶片段(crystallizable fragment, Fc)结构域在调节免疫应答中同样发挥着关键作用。Fc结构域可与效应细胞[如自然杀伤细胞(natural killer cells, NK cells)、巨噬细胞、中性粒细胞和树突状细胞(dendritic cells, DCs)]表面的Fc受体(Fc receptors, FcRs)或补体受体结合，激活多条先天免疫信号通路，并介导多种非中和性抗病毒效应。这些效应功能包括抗体依赖的细胞介导的细胞毒作用(antibody-dependent cellular cytotoxicity, ADCC)、抗体依赖性细胞吞噬作用(antibody-dependent cellular phagocytosis, ADCP)、抗体依赖性补体沉积作用(antibody-dependent complement deposition, ADCD)以及补体依赖性细胞毒作用(complement-dependent cytotoxicity, CDC)等。尽管Fc效应功能的检测相较于中和抗体滴度测定更为复杂，但其在疫苗诱导的保护效应中的重要性日益凸显。本文系统综述了抗体Fc结构域介导的免疫效应机制，探讨了其在病毒性疫苗免疫保护过程中的功能，并总结了当前主流的Fc功能检测方法，为新型病毒性疫苗的研发与免疫效果评价提供理论依据与技术参考。

Abstract:

Antibodies serve as critical effector molecules in mediating vaccine-induced protection. While antibody-mediated immunity has traditionally been attributed primarily to neutralization, where the fragment antigen-binding (Fab) domain blocks viral entry by preventing the interaction between viruses and host cells, accumulating evidence underscores the pivotal role of the crystallizable fragment (Fc) domain in orchestrating broader immune responses. By interacting with Fc receptors or complement receptors on effector cells such as natural killer cells, macrophages, neutrophils, and dendritic cells, the Fc domain activates multiple innate immune pathways and elicits a spectrum of non-neutralizing antiviral effector functions. These include antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), antibody-dependent complement deposition (ADCD), and complement-dependent cytotoxicity (CDC). Although the evaluation of Fc-mediated functions is more complex than the measurement of neutralizing antibody titers, the contribution of such functions to vaccine efficacy is increasingly recognized. This review provides a comprehensive overview of Fc-mediated immune effector mechanisms, highlights their critical roles in antiviral vaccine-induced protection, and summarizes recent advances in Fc function assays, with the aim of supporting the rational design and immunogenicity evaluation of next-generation viral vaccines.