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[HIV特异性抗体抗病毒感染的免疫效应及机制]

[Immune Effects and Mechanisms of HIV-specific Antibodies Against Viral Infection].

作者信息

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

出版信息

Bing Du Xue Bao. 2016 Nov;32(6):830-8.

Abstract

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.

摘要

广泛中和抗体(bNAbs)已在非人灵长类动物和人源化小鼠模型的实验性攻毒中显示出保护作用。最近,bNAbs 3BNC117和VRC01在一项I期临床试验中进行了评估,并被证明可降低未接受抗逆转录病毒治疗的人类免疫缺陷病毒(HIV)-1感染个体的血浆病毒血症。然而,通过疫苗接种诱导这类抗体极其困难。此外,在RV144疫苗试验中观察到的31%的保护率,尽管血液样本中未检测到bNAbs,但这表明控制HIV感染和复制的抗体的其他抑制功能具有重要作用。越来越多的证据表明,免疫球蛋白-G Fcγ受体介导的对黏膜部位存在的抗体的抑制作用可能对HIV的黏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此类Fc受体,并且可能在早期黏膜传播中起决定性作用,因为它们被认为是黏膜部位HIV的首个靶标。因此,除了bNAbs之外,还应开发涉及诱导此类非中和抑制性抗体和其他抗病毒功能的新疫苗策略。

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