Laboratory of Experimental Immunology, Institute of Virology, University Hospital Cologne, Fürst-Pückler-Str. 56, 50935, Cologne, Germany.
German Center for Infection Research, Partner-Site Bonn-Cologne, Cologne, Germany.
Retrovirology. 2018 Nov 16;15(1):73. doi: 10.1186/s12977-018-0455-9.
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.
新型广谱中和抗体有望用于预防和治疗 HIV-1 感染。临床前研究结果鼓励在健康人群和 HIV-1 感染者中评估这些抗体。在首次临床试验中,高效广谱中和抗体通过降低病毒载量和延迟中断抗逆转录病毒治疗的个体病毒反弹时间,证明了其安全性和显著的抗病毒活性。虽然新兴的抗体耐药病毒变异表明抗体单药治疗存在局限性,但正在研究增强人类广谱中和抗体疗效的策略。这些策略包括使用抗体组合来防止病毒逃逸、抗体修饰来增加半衰期以及联合使用潜伏逆转剂来靶向 HIV-1 的细胞储库。我们提供了广谱中和 HIV-1 抗体的临床前和临床研究结果的概述,讨论了它们的意义,并强调了正在向人体推进的方法。