Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies
Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies
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DOI：
10.1126/science.1111781
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发表时间：
2005-06-24
期刊：
影响因子：
56.9
通讯作者：
Alam, SM
中科院分区：
文献类型：
--
作者：
Haynes, BF;Fleming, J;Alam, SM
设计一种能够诱导广泛反应性中和抗体的人类免疫缺陷病毒-1（HIV-1）免疫原是HIV-1疫苗开发的主要目标。尽管存在广泛中和HIV-1的罕见的人单克隆抗体（mAb），但HIV-1包膜免疫原不诱导这些抗体特异性。在这里，我们证明了两个最广泛的反应性HIV-1包膜gp 41人单克隆抗体，2175和4 E10，是多特异性自身抗体与磷脂心磷脂反应。因此，目前的HIV-1疫苗可能不会诱导这些类型的抗体，因为自身抗原模拟病毒的保守膜近端表位。这些结果可能对使用HIV-1疫苗产生有效的中和抗体反应具有重要意义。
The design of a human immunodeficiency virus-1 (HIV-1) immunogen that can induce broadly reactive neutralizing antibodies is a major goal of HIV-1 vaccine development. Although rare human monoclonal antibodies (mAbs) exist that broadly neutralize HIV-1, HIV-1 envelope immunogens do not induce these antibody specificities. Here we demonstrate that the two most broadly reactive HIV-1 envelope gp41 human mAbs, 2175 and 4E10, are polyspecific autoantibodies reactive with the phospholipid cardiolipin. Thus, current HIV-1 vaccines may not induce these types of antibodies because of autoantigen mimicry of the conserved membrane-proximal epitopes of the virus. These results may have important implications for generating effective neutralizing, antibody responses by using HIV-1 vaccines.