hiv特异性抗体抗病毒感染的免疫效应和机制

Bin Su, Lan Li, Danlei Mou, Christiane Moog, Hao Wu, Tong Zhang
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摘要

广泛中和抗体(bNAbs)在非人灵长类动物和人源化小鼠模型中显示出保护作用。最近,bNAbs 3BNC117和vrc01在一项i期临床试验中进行了评估,并显示出在未接受抗逆转录病毒治疗的人类免疫缺陷病毒(HIV)-1感染个体中降低血浆病毒血症。然而,通过接种疫苗来诱导这些类型的抗体是极其困难的。此外,在血液样本中检测不到bNAbs的情况下,RV144疫苗试验中观察到的31%的保护表明,控制HIV感染和复制的抗体具有额外抑制功能的重要作用。越来越多的证据表明,免疫球蛋白- gfcγ受体介导的粘膜部位抗体抑制可能对HIV的粘膜传播具有保护作用。树突状细胞和巨噬细胞在其表面表达这样的Fc受体,并且可能在早期粘膜传播中起决定性作用,因为它们被认为是粘膜部位的第一个HIV靶点。因此,除了bnab外,还应该开发新的疫苗接种策略,包括诱导这种非中和性抑制抗体和其他抗病毒功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Immune Effects and Mechanisms of HIV-specific Antibodies Against Viral Infection].

Broadly neutralizing antibodies (bNAbs) have demonstrated a protective role from experimental challenge in non-human primates and humanized mouse models. Recently, bNAbs 3BNC117 and VRC01were assessed in a phase-I clinical trial, and were shown to lower plasma viremia in human immunodeficiency virus(HIV)-1-infected individuals not receiving antiretroviral therapy. However, induction of these types of antibodies by vaccination iS extremely difficult. Moreover, the 31% protection observed in the RV144 vaccine trial in the absence of detectable bNAbs in blood samples suggested the important role of additional inhibitory functions of the antibodies that control infection and replication of HIV. Increasing evidence suggests that immunoglobulin-G Fcγ receptor-mediated inhibition of antibodies present at the mucosal site may have a protective role against mucosal transmission of HIV. Dendritic cells and macrophages express such Fc receptors on their surface, and may have a decisive role in early mucosal transmission because they have been proposed to be the first HIV target at the mucosal site. Therefore, new vaccination strategies involving induction of such non-neutralizing inhibitory antibodies and other antiviral functions, in addition to bNAbs, should be developed.

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