Wines Bruce D, Billings Hugh, Mclean Milla R, Kent Stephen J, Hogarth P Mark
Centre for Biomedical Research, Burnet Institute, Melbourne, Vic 3004, Australia.
Department of Immunology, Monash University Central Clinical School, Melbourne, Victoria 3004, Australia.
Curr HIV Res. 2017;15(3):202-215. doi: 10.2174/1570162X15666170320112247.
There is now intense interest in the role of HIV-specific antibodies and the engagement of FcγR functions in the control and prevention of HIV infection. The analyses of the RV144 vaccine trial, natural progression cohorts, and macaque models all point to a role for Fc-dependent effector functions, such as cytotoxicity (ADCC) or phagocytosis (ADCP), in the control of HIV. However, reliable assays that can be reproducibly used across different laboratories to measure Fcdependent functions, such as antibody dependent cellular cytotoxicity (ADCC) are limited.
This brief review highlights the importance of Fc properties for immunity to HIV, particularly via FcγR diversity and function. We discuss assays used to study FcR mediated functions of HIV-specific Ab, including our recently developed novel cell-free ELISA using homo-dimeric FcγR ectodomains to detect functionally relevant viral antigen-specific antibodies.
The binding of these dimeric FcγR ectodomains, to closely spaced pairs of IgG Fc, mimics the engagement and cross-linking of Fc receptors by IgG opsonized virions or infected cells as the essential prerequisite to the induction of Ab-dependent effector functions. The dimeric FcγR ELISA reliably correlates with ADCC in patient responses to influenza. The assay is amenable to high throughput and could be standardized across laboratories.
We propose the assay has broader implications for the evaluation of the quality of antibody responses in viral infections and for the rapid evaluation of responses in vaccine development campaigns for HIV and other viral infections.
目前，人们对HIV特异性抗体的作用以及FcγR功能参与HIV感染的控制和预防极为关注。RV144疫苗试验、自然病程队列研究以及猕猴模型的分析均表明，Fc依赖性效应功能，如细胞毒性（ADCC）或吞噬作用（ADCP），在HIV控制中发挥作用。然而，能够在不同实验室中可重复使用以测量Fc依赖性功能（如抗体依赖性细胞毒性（ADCC））的可靠检测方法有限。
本简要综述强调了Fc特性对HIV免疫的重要性，特别是通过FcγR的多样性和功能。我们讨论了用于研究HIV特异性抗体的FcR介导功能的检测方法，包括我们最近开发的使用同型二聚体FcγR胞外域检测功能相关的病毒抗原特异性抗体的新型无细胞ELISA。
这些二聚体FcγR胞外域与紧密相邻的IgG Fc对结合，模拟了IgG调理的病毒颗粒或感染细胞对Fc受体的结合和交联，这是诱导抗体依赖性效应功能的必要前提。二聚体FcγR ELISA与患者对流感的反应中的ADCC可靠相关。该检测方法适用于高通量，并且可以在不同实验室间进行标准化。
我们认为该检测方法对评估病毒感染中抗体反应的质量以及快速评估HIV和其他病毒感染疫苗研发活动中的反应具有更广泛的意义。
