Independent evolution of Fc- and Fab-mediated HIV-1-specific antiviral antibody activity following acute infection.
Independent evolution of Fc- and Fab-mediated HIV-1-specific antiviral antibody activity following acute infection.
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急性感染后FC和FAB介导的HIV-1特异性抗体活性的独立进化。
DOI：
10.1002/eji.201344305
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发表时间：
2014-10
影响因子：
5.4
通讯作者：
Alter, Galit
中科院分区：
文献类型：
--
作者：
Dugast, Anne-Sophie;Stamatatos, Leonidas;Tonelli, Andrew;Suscovich, Todd J.;Licht, Anna F.;Mikell, Iliyana;Ackerman, Margaret E.;Streeck, Hendrik;Klasse, P. J.;Moore, John P.;Alter, Galit
Fc相关的抗体活性，如抗体依赖性细胞毒性（ADCC），或更广泛地说，抗体介导的细胞病毒抑制（ADCVI），在抑制早期SIV病毒复制中发挥作用，在人类长期感染的非进展者中富集，并可能有助于保护免受感染。然而，很少有人知道的机制，这种体液免疫反应是自然诱导感染后。在本文中，我们重点关注功能性抗体应答的早期演变，主要由抗体的Fc部分驱动，而结合和中和抗体应答的演变主要由抗体结合片段（Fab）驱动。我们发现，ADCVI/ADCC诱导的反应在人类急性HIV-1感染后迅速产生，感染后约6个月达到峰值，但在持续免疫激活的情况下迅速衰减，因为Fab相关活动持续增加。此外，Fc活性的丧失与HIV特异性IgG 3应答的丧失同步发生。我们的数据强烈表明，Fc和Fab相关的抗体功能调制在一个不同的方式急性HIV感染后。因此，旨在最佳诱导两组抗病毒抗体活性的疫苗接种策略可能需要微调炎症反应。
Fc-related antibody activities, such as antibody-dependent cellular cytotoxicity (ADCC), or more broadly, antibody-mediated cellular viral inhibition (ADCVI), play a role in curbing early SIV viral replication, are enriched in human long-term infected non-progressors, and could potentially contribute to protection from infection. However, little is known about the mechanism by which such humoral immune responses are naturally induced following infection. Here we focused on the early evolution of the functional antibody response, largely driven by the Fc portion of the antibody, in the context of the evolving binding and neutralizing antibody response, which is driven mainly by the antibody binding fragment (Fab). We show that ADCVI/ADCC-inducing responses in humans are rapidly generated following acute HIV-1 infection, peak at approximately 6 months post-infection, but decay rapidly in the setting of persistent immune activation, as Fab-related activities persistently increase. Moreover, the loss of Fc activity occurred in synchrony with a loss of HIV-specific IgG3 responses. Our data strongly suggest that Fc- and Fab-related antibody functions are modulated in a distinct manner following acute HIV infection. Vaccination strategies intended to optimally induce both sets of antiviral antibody activities may, therefore, require a fine-tuning of the inflammatory response.
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