Antibody-mediated prevention and treatment of HIV-1 infection.

Antibody-mediated prevention and treatment of HIV-1 infection.
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DOI:
10.1186/s12977-018-0455-9
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发表时间:
2018-11-16
期刊:
影响因子:
3.3
通讯作者:
Klein F
Klein F
中科院分区:
医学2区
文献类型:
--
作者:
Gruell H;Klein F

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靶向HIV-1的新型广泛中和抗体有望用于预防和治疗HIV-1感染。临床前结果鼓励在健康和HIV-1感染者中评价这些抗体。在第一次临床试验中,高度有效的广泛中和抗体已经证明了它们的安全性和显著的抗病毒活性,通过减少病毒血症和延迟中断抗逆转录病毒治疗的个体的病毒反弹时间。虽然新出现的抗体耐药病毒变异体表明了抗体单一疗法的局限性,但增强人类广泛中和抗体疗效的策略正在研究中。这些措施包括使用抗体组合来防止病毒逃逸,抗体修饰以增加半衰期,以及共同施用潜伏期逆转剂以靶向HIV-1的细胞储库。我们提供了广泛的HIV-1中和抗体的临床前和临床研究的结果的概述,讨论了它们的影响,并强调了正在进行的进展到人类的方法。
Novel broadly neutralizing antibodies targeting HIV-1 hold promise for their use in the prevention and treatment of HIV-1 infection. Pre-clinical results have encouraged the evaluation of these antibodies in healthy and HIV-1-infected humans. In first clinical trials, highly potent broadly neutralizing antibodies have demonstrated their safety and significant antiviral activity by reducing viremia and delaying the time to viral rebound in individuals interrupting antiretroviral therapy. While emerging antibody-resistant viral variants have indicated limitations of antibody monotherapy, strategies to enhance the efficacy of broadly neutralizing antibodies in humans are under investigation. These include the use of antibody combinations to prevent viral escape, antibody modifications to increase the half-life and the co-administration of latency-reversing agents to target the cellular reservoir of HIV-1. We provide an overview of the results of pre-clinical and clinical studies of broadly HIV-1 neutralizing antibodies, discuss their implications and highlight approaches for the ongoing advancement into humans.
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