Detection of antibody-dependent complement-mediated inactivation of both autologous and heterologous virus in primary human immunodeficiency virus type I infection

Detection of antibody-dependent complement-mediated inactivation of both autologous and heterologous virus in primary human immunodeficiency virus type I infection
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DOI:
10.1128/jvi.79.5.2823-2830.2005
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发表时间:
2005-03-01
影响因子:
5.4
通讯作者:
Mcknight, A
Mcknight, A
中科院分区:
医学2区
文献类型:
--
作者:
Aasa-Chapman, MMI;Holuigue, S;Mcknight, A

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针对1型人类免疫缺陷病毒(HIV - 1)的特异性CD8 T细胞应答在初次感染时被诱导产生,并且对早期病毒复制的控制起到重要作用。中和抗体在抑制初次病毒血症中的重要性受到质疑,因为它们通常出现得晚得多。然而,抗包膜抗体与病毒血症高峰同时甚至在其之前产生。我们确定了这类抗体是否可能通过补体介导的失活作用(CMI)来控制病毒血症。在所研究的7名患者中,每一名患者都在病毒血症高峰时或之后不久出现了能够进行CMI的抗体,同时检测到病毒特异性T细胞应答。CMI对自体和异体HIV - 1分离株均有效。经典途径的激活和病毒的直接裂解至少是部分原因。由于免疫球蛋白G(IgG)抗体触发了CMI,通过疫苗接种也可能诱导出特异性记忆B细胞。因此,应该考虑采用能诱导出具有CMI能力的IgG抗体的疫苗接种策略。
Specific CD8 T-cell responses to human immunodeficiency virus type 1 (HIV-1) are induced in primary infection and make an important contribution to the control of early viral replication. The importance of neutralizing antibodies in containing primary viremia is questioned because they usually arise much later. Nevertheless antienvelope antibodies develop simultaneously with, or even before, peak viremia. We determined whether such antibodies might control viremia by complement-mediated inactivation (CMI). In each of seven patients studied, antibodies capable of CMI appeared at or shortly after the peak in viremia, concomitantly with detection of virus-specific T-cell responses. The CMI was effective on both autologous and heterologous HIV-1 isolates. Activation of the classical pathway and direct viral lysis were at least partly responsible. Since immunoglobulin G (IgG)-antibodies triggered the CMI, specific memory B cells could also be induced by vaccination. Thus, consideration should be given to vaccination strategies that induce IgG antibodies capable of CMI.