Enhancing antibodies in HIV infection
Enhancing antibodies in HIV infection
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DOI：
10.1017/s0031182097001819
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发表时间：
1997-01-01
期刊：
影响因子：
2.4
通讯作者：
Füst, G
中科院分区：
文献类型：
--
作者：
Füst, G
本文综述了HIV感染抗体依赖性增强（ADE）的发现历史、机制及临床意义。ADE主要有两种形式：(a)补体介导的抗体依赖性增强（C-ADE）和(b)补体非依赖型Fc受体依赖性ADE （fr -ADE）。负责c - ade介导抗体产生的最重要的表位存在于gp41的免疫优势区，而介导fr - ade的抗体主要与gp120的V3环反应。对于体外ADE的解释，至少有三种根本不同的假设：(a) hiv抗体（补体）复合物与FcR或补体受体携带细胞的粘附性增加；(b)沉积在hiv病毒粒子上的补体片段促进hiv靶细胞融合；(c)补体激活产物可能对靶细胞具有非特异性刺激作用，从而增强病毒的产生。FcR-ADE和C-ADE的体外测定主要采用携带for和携带补体受体的细胞系；没有努力使这些方法标准化。一些数据支持FcR-ADE和C-ADE可能的临床意义：(a)横断面和纵向研究表明，FcR-ADE和C-ADE介导抗体的数量与艾滋病毒疾病的临床、免疫学和病毒学进展之间存在相关性；(b) ADE可能促进艾滋病毒-1母婴传播；(c)根据动物模型实验，ADE存在，并可能改变SIV（猿类免疫缺陷）感染的过程。作者对C-ADE的体内作用机制提出了新的假设。根据这一假设，c - ade介导的抗体通过增强HIV的传播从而促进HIV疾病的进展来发挥作用。最后，根据动物实验和人体临床试验的观察结果，不能排除在接种了HIV-1候选疫苗的志愿者中可能产生ade介导抗体，减少有益效果或可能有害。
The author has summarized the history of discovery, the mechanism and the clinical significance of antibody-dependent enhancement (ADE) of HIV infection. ADE has two major forms: (a) complement-mediated antibody-dependent enhancement (C-ADE) and (b) complement-independent Fc receptor-dependent ADE (FcR-ADE). The most important epitope responsible for the development of C-ADE-mediating antibodies is present in the immunodominant region of gp41 while antibodies mediating FcR-ADE react mainly with V3 loop of gp120. There are at least three fundamentally different hypotheses for the explanation of ADE in vitro : (a) increased adhesion of HIV-antibody-(complement) complexes to FcR or complement receptor carrying cells; (b) facilitation of HIV-target cell fusion by complement fragment deposited on the HIV-virions and (c) complement activation products may have a non-specific stimulatory effect on target cells resulting in enhanced virus production. FcR-ADE and C-ADE have been measured in vitro mostly by using FOR-carrying and complement receptor-carrying cell lines, respectively; no efforts have bees made to standardize these methods. Several data support the possible clinical significance of FcR-ADE and C-ADE: (a) Cross-sectional and longitudinal studies indicate a correlation between the amounts of FcR-ADE and C-ADE-mediating antibodies and clinical, immunological and virological progression of the HIV-disease; (b) ADE may facilitate maternal-infant HIV-1 transmission; (c) According to experiments in animal models, ADE are present and may modify the course of SIV (simian immunodeficiency) infection as well. The author raises a new hypothesis on the mechanism of the in vivo effect of C-ADE. According to the hypothesis, C-ADE-mediating antibodies exert their effect through enhancement of HIV propagation and consequent facilitation of the progression of HIV disease. Finally, according to observations from animal experiments and human clinical trials it cannot be excluded that ADE-mediating antibodies may develop, diminish the beneficial effect or may be harmful in volunteers vaccinated with HIV-1 candidate vaccines.