HIV therapy by a combination of broadly neutralizing antibodies in humanized mice.
HIV therapy by a combination of broadly neutralizing antibodies in humanized mice.
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HIV-1 人类抗体可以在体外中和多种病毒分离株，并保护非人类灵长类动物免受感染。先前的研究表明，抗体对病毒施加选择性压力，但会在短时间内出现逃逸变异。然而，这些实验是在最近发现更有效的抗 HIV-1 抗体并通过基于结构的设计对其进行改进之前进行的。在这里，我们重新审视被动抗体转移作为 HIV-1 感染人源化小鼠 (hu-mice) 的治疗方式。尽管 HIV-1 可以逃避抗体单一疗法，但广泛中和抗体 (bNAb) 的组合可以有效控制 HIV-1 感染并将病毒载量抑制到检测水平以下。此外，与抗逆转录病毒疗法 (ART) 相比，抗体的半衰期较长，可在停止治疗后平均 60 天实现病毒血症控制。因此，强效单克隆抗体的组合可以有效控制 hu-mice 中的 HIV-1 复制，并且应该重新审查其作为 HIV-1 感染个体的治疗方式。
Human antibodies to HIV-1 can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice (hu-mice). Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies (bNAbs) can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy (ART), the longer half-life of antibodies led to viremic control for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in hu-mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals.