Recent insights into Fc-mediated effector responses to HIV-1.
Recent insights into Fc-mediated effector responses to HIV-1.
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DOI：
10.1097/coh.0000000000000638
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发表时间：
2020-09
影响因子：
4.1
通讯作者：
Ackerman ME
中科院分区：
文献类型：
--
作者：
Carpenter MC;Ackerman ME
最近的工作定义Fc介导的效应器功能的病毒控制和保护免受感染的总结和考虑沿着新的战略，以推动强大的Fc介导的反应。在新的人类和非人类灵长类动物疫苗试验以及自然感染研究中，有时观察到Fc介导的效应子应答与感染风险降低或临床结局改善相关，表明这些应答在HIV-1预防和治疗中具有潜在作用。最近的亮点包括使用ADCC致敏CD 4 i模拟化合物，新型V1 V2免疫原，被动转移研究和疫苗方案，成功地引发Fc介导的反应，并报告在NHP的挑战研究中降低感染风险。最后，对HIV特异性抗体IgG 3形式的详细研究报告称，中和和Fc介导的应答相对于更普遍的IgG 1亚类都可以增加。中和和Fc介导的应答的成功协调可能对通过主动和被动疫苗接种减少HIV-1感染的目标做出关键贡献。新的研究继续强调Fc介导的抗体应答作为感染风险降低的相关因素的重要性，并表明增强的吞噬作用是与人IgG 3应答相关的感染风险降低的潜在机制。最近的研究结果可能有助于指导旨在特异性利用抗体效应子功能的疗法和疫苗的合理设计。
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 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 ADCC-sensitizing CD4i 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.