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在开始接受抗逆转录病毒疗法时使用广泛中和抗 HIV-1 抗体可维持长期的 CD8 T 细胞免疫。

Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8 T cell immunity.

机构信息

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.

出版信息

Nat Commun. 2022 Oct 29;13(1):6473. doi: 10.1038/s41467-022-34171-2.

Abstract

In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8 T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in cellular immunity were directly correlated to pre-treatment 3BNC117-sensitivity. Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8 T cell responses that are associated with ART-free virologic control.

摘要

在感染猴免疫缺陷病毒(SHIV)的非人类灵长类动物中,针对该病毒的广泛中和抗体(bNAb)似乎能刺激 T 细胞免疫。为了确定这一现象是否也发生在人类中,我们纵向测量了开始接受抗病毒治疗(ART)的个体中 HIV-1 的特异性细胞免疫,这些个体接受了或未接受辅助性 bNAb 3BNC117 治疗。通过使用激活诱导标志物(AIM)检测和干扰素-γ释放,我们观察到,在开始 ART 后 3 和 12 个月,接受辅助性 3BNC117 治疗的个体中,Pol 和 Gag 特异性 CD8 T 细胞的频率以及 Gag 诱导的干扰素-γ反应明显更高,与单独接受 ART 治疗相比。细胞免疫的观察到的变化与治疗前 3BNC117 的敏感性直接相关。值得注意的是,在长达 4 年的治疗中断期间,HIV-1 特异性免疫的增加与部分或完全无 ART 的病毒学控制相关。我们的研究结果表明,在开始 ART 的同时进行 bNAb 治疗可以维持 HIV-1 特异性 CD8 T 细胞反应,与无 ART 的病毒学控制相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/501e/9617872/ed7a7810787d/41467_2022_34171_Fig1_HTML.jpg

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