Departments of Otolaryngology-Head and Neck Surgery and Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA.
Department of Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110, USA.
Cell Rep. 2022 May 17;39(7):110815. doi: 10.1016/j.celrep.2022.110815.
Although generating high neutralizing antibody levels is a key component of protective immunity after acute viral infection or vaccination, little is known about why some individuals generate high versus low neutralizing antibody titers. Here, we leverage the high-dimensional single-cell profiling capacity of mass cytometry to characterize the longitudinal cellular immune response to Zika virus (ZIKV) infection in viremic blood donors in Puerto Rico. During acute ZIKV infection, we identify widely coordinated responses across innate and adaptive immune cell lineages. High frequencies of multiple activated cell types during acute infection are associated with high titers of ZIKV neutralizing antibodies 6 months post-infection, while stable immune features suggesting a cytotoxic-skewed immune set point are associated with low titers. Our study offers insight into the coordination of immune responses and identifies candidate cellular biomarkers that may offer predictive value in vaccine efficacy trials aimed at inducing high levels of antiviral neutralizing antibodies.
尽管产生高中和抗体水平是急性病毒感染或接种疫苗后保护性免疫的关键组成部分，但对于为什么有些人产生高中和抗体滴度而有些人产生低中和抗体滴度知之甚少。在这里，我们利用液滴式多重流式细胞术的高维单细胞分析能力，来描述波多黎各病毒血症献血者感染寨卡病毒（ZIKV）后的纵向细胞免疫反应。在急性 ZIKV 感染期间，我们发现先天免疫和适应性免疫细胞谱系之间存在广泛的协调反应。在急性感染期间，多种激活的细胞类型高频出现与感染后 6 个月的 ZIKV 中和抗体高滴度相关，而稳定的免疫特征表明细胞毒性偏向的免疫设定点与低滴度相关。我们的研究提供了对免疫反应协调的深入了解，并确定了候选细胞生物标志物，这些标志物可能在旨在诱导高水平抗病毒中和抗体的疫苗功效试验中提供预测价值。
