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通过在体内对HIV-1抗体的广泛中和,增强了HIV-1感染细胞的清除

Ching-Lan Lu¹, Dariusz K Murakowski², Stylianos Bournazos³

¹Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY 10065, USA.

Science (New York, N.Y.)

|May 21, 2016

概括

广泛中和抗体可以消除感染HIV-1的细胞. 这种被动免疫治疗方法使用抗体向和清除受感染的CD4 ((+) T细胞,需要Fcγ受体激活才能有效.

科学领域:

免疫学
病毒学
药理学

背景情况:

抗逆转录病毒药物和抗体是通过破坏病毒生命周期来控制HIV-1感染的关键.
抗体还可以激活宿主免疫细胞去消灭受感染的细胞.
广泛中和抗体3BNC117的被动使用显示出超越病毒清除的潜力,表明受感染细胞的消除.

研究的目的:

研究大致中和抗体 (bNAbs) 有助于艾滋病毒-1 感染细胞清除的机制.
为了确定bNAbs是否可以加速携带HIV-1的CD4 ((+) T细胞的清除.
探索Fcγ受体参与感染细胞的抗体介导清除的作用.

主要方法:

使用人类免疫细胞植入的人类小鼠模型.
向受感染的人类化小鼠注射来自患者的HIV-1分离物.
评估被动施用广泛中和抗体对受感染的CD4 ((+) T细胞半衰期的影响.
研究了Fcγ受体对抗体介导细胞清除的必要性.

主要成果:

广泛中和抗体有效地向感染患者衍生的HIV-1的CD4T细胞.
使用bNAbs的被动免疫疗法显著降低了受感染的CD4 ((+) T细胞的体内半衰期.
对于抗体介导的感染细胞清除加速来说,Fcγ受体的参与是必不可少的.

结论:

广泛中和抗体可以积极消除HIV-1感染细胞,而不仅仅是中和自由病毒.
通过依赖Fcγ受体的机制,被动免疫疗法加速了HIV-1感染细胞的清除.
这些发现支持基于抗体的疗法在消灭HIV-1存储库方面的潜力.

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