Thayer School of Engineering, Dartmouth College.
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
Curr Opin HIV AIDS. 2020 Sep;15(5):282-289. doi: 10.1097/COH.0000000000000638.
Recent work defining Fc-mediated effector functions for both viral control and protection against infection is summarized and considered along with new strategies to drive robust Fc-mediated responses.
In new human and nonhuman primate (NHP) vaccine trials as well as studies of natural infection, Fc-mediated effector responses have sometimes been observed to correlate with decreased risk of infection or with better clinical outcomes, suggesting a potential role for these responses in HIV-1 prevention and therapy. Recent highlights include use of antibody-dependent cellular cytotoxicity-sensitizing CD4-induced mimetic compounds, novel V1V2 immunogens, passive transfer studies, and vaccine regimens that successfully elicited Fc-mediated responses and were reported to decrease risk of infection in challenge studies in NHPs. Lastly, detailed studies of IgG3 forms of HIV-specific antibodies have reported that both neutralizing and Fc-mediated responses can be increased relative to the more prevalent IgG1 subclass.
Successful harmonization of neutralizing and Fc-mediated responses may make key contributions to the goal of reducing HIV-1 infection via active and passive vaccination. New studies continue to highlight the importance of Fc-mediated antibody responses as correlates of decreased risk of infection and suggest enhanced phagocytosis is a potential mechanism of reduced risk of infection associated with human IgG3 responses. Results from recent studies may help guide the rational design of therapies and vaccines that aim to specifically leverage antibody effector function.
总结了最近关于 Fc 介导的效应功能在病毒控制和感染保护方面的研究，并结合新策略来促进强大的 Fc 介导的反应进行了讨论。
在新的人体和非人灵长类动物（NHP）疫苗试验以及自然感染研究中，Fc 介导的效应反应有时与降低感染风险或更好的临床结果相关，这表明这些反应可能在 HIV-1 的预防和治疗中发挥作用。最近的亮点包括使用抗体依赖性细胞毒性敏感的 CD4 诱导模拟化合物、新型 V1V2 免疫原、被动转移研究以及疫苗方案，这些方案成功地引起了 Fc 介导的反应，并据报道在 NHP 的挑战研究中降低了感染风险。最后，对 HIV 特异性抗体 IgG3 形式的详细研究报告称，与更常见的 IgG1 亚类相比，中和和 Fc 介导的反应都可以增加。
成功协调中和和 Fc 介导的反应可能对通过主动和被动免疫接种降低 HIV-1 感染的目标做出重要贡献。新的研究继续强调 Fc 介导的抗体反应作为降低感染风险的相关因素的重要性，并表明增强吞噬作用可能是与人类 IgG3 反应相关的感染风险降低的潜在机制。最近研究的结果可能有助于指导旨在专门利用抗体效应功能的治疗和疫苗的合理设计。
