Edgar Julia E, Bournazos Stylianos
The London School of Hygiene and Tropical Medicine, London, UK.
The Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, New York, USA.
Immunol Rev. 2024 Nov;328(1):221-242. doi: 10.1111/imr.13393. Epub 2024 Sep 13.
Advances in antibody technologies have resulted in the development of potent antibody-based therapeutics with proven clinical efficacy against infectious diseases. Several monoclonal antibodies (mAbs), mainly against viruses such as SARS-CoV-2, HIV-1, Ebola virus, influenza virus, and hepatitis B virus, are currently undergoing clinical testing or are already in use. Although these mAbs exhibit potent neutralizing activity that effectively blocks host cell infection, their antiviral activity results not only from Fab-mediated virus neutralization, but also from the protective effector functions mediated through the interaction of their Fc domains with Fcγ receptors (FcγRs) on effector leukocytes. Fc-FcγR interactions confer pleiotropic protective activities, including the clearance of opsonized virions and infected cells, as well as the induction of antiviral T-cell responses. However, excessive or inappropriate activation of specific FcγR pathways can lead to disease enhancement and exacerbated pathology, as seen in the context of dengue virus infections. A comprehensive understanding of the diversity of Fc effector functions during infection has guided the development of engineered antiviral antibodies optimized for maximal effector activity, as well as the design of targeted therapeutic approaches to prevent antibody-dependent enhancement of disease.
抗体技术的进步推动了基于抗体的强效治疗药物的开发，这些药物在治疗传染病方面已被证明具有临床疗效。目前，几种单克隆抗体（mAb）正在进行临床试验或已投入使用，主要针对如严重急性呼吸综合征冠状病毒2（SARS-CoV-2）、人类免疫缺陷病毒1型（HIV-1）、埃博拉病毒、流感病毒和乙型肝炎病毒等病毒。尽管这些单克隆抗体表现出强大的中和活性，能有效阻断宿主细胞感染，但其抗病毒活性不仅源于Fab介导的病毒中和作用，还源于其Fc结构域与效应白细胞上的Fcγ受体（FcγR）相互作用介导的保护性效应功能。Fc-FcγR相互作用赋予多种保护活性，包括清除被调理素包被的病毒粒子和受感染细胞，以及诱导抗病毒T细胞反应。然而，特定FcγR途径的过度或不适当激活可导致疾病加重和病理恶化，如在登革病毒感染的情况下所见。对感染期间Fc效应功能多样性的全面理解，为开发针对最大效应活性进行优化的工程化抗病毒抗体以及设计预防抗体依赖性疾病增强的靶向治疗方法提供了指导。
