Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19
Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19
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DOI：
10.1038/s41591-020-0995-0
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发表时间：
2020-07-13
期刊：
影响因子：
82.9
通讯作者：
Wheatley, Adam K.
中科院分区：
文献类型：
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作者：
Juno, Jennifer A.;Tan, Hyon-Xhi;Wheatley, Adam K.
严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）大流行极大地加快了全球疫苗开发工作（1-3），其中大多数针对病毒“刺突”糖蛋白(S)。S定位于病毒粒子表面，介导细胞受体血管紧张素转换酶2 （ACE2）的识别（4-6）。激发阻断S-ACE2相互作用的中和抗体（7-9），或间接阻止膜融合（10），构成了疫苗诱导保护的一种有吸引力的方式（11）。然而，尽管基于原型的疫苗在动物模型中显示出希望（12-14），但S在人类中的免疫原性尚不清楚。在这项研究中，我们研究了2019冠状病毒病（COVID-19）康复患者的体液和循环滤泡辅助T细胞（cTFH）免疫对峰值的影响。我们发现s特异性抗体、记忆B细胞和cTFH在SARS-CoV-2感染后一致被激发，这表明了强大的体液免疫，并与血浆中和活性呈正相关。S受体结合域特异性的B细胞或cTFH的频率相对较低。值得注意的是，s特异性cTFH的表型分化了具有强效中和反应的受试者，为进入临床的基于s的疫苗提供了潜在的效力生物标志物。总体而言，尽管从COVID-19康复的患者表现出对S有效免疫识别的多种特征，但观察到的广泛中和活性表明，疫苗可能需要有选择性地靶向最有效中和表位的策略。在一组康复的COVID-19患者中，病毒尖刺特异性抗体一致被激发，但中和活性变化很大，并且与CCR6(+)CXCR3（-）尖刺特异性循环滤泡辅助T细胞的比例呈负相关。
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts(1-3), most targeting the viral 'spike' glycoprotein (S). S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2)(4-6). Eliciting neutralizing antibodies that block S-ACE2 interaction(7-9), or indirectly prevent membrane fusion(10), constitute an attractive modality for vaccine-elicited protection(11). However, although prototypic S-based vaccines show promise in animal models(12-14), the immunogenic properties of S in humans are poorly resolved. In this study, we characterized humoral and circulating follicular helper T cell (cTFH) immunity against spike in recovered patients with coronavirus disease 2019 (COVID-19). We found that S-specific antibodies, memory B cells and cTFH are consistently elicited after SARS-CoV-2 infection, demarking robust humoral immunity and positively associated with plasma neutralizing activity. Comparatively low frequencies of B cells or cTFH specific for the receptor binding domain of S were elicited. Notably, the phenotype of S-specific cTFH differentiated subjects with potent neutralizing responses, providing a potential biomarker of potency for S-based vaccines entering the clinic. Overall, although patients who recovered from COVID-19 displayed multiple hallmarks of effective immune recognition of S, the wide spectrum of neutralizing activity observed suggests that vaccines might require strategies to selectively target the most potent neutralizing epitopes.In a cohort of recovered patients with COVID-19, virus spike-specific antibodies were consistently elicited, but neutralizing activity was highly variable and inversely correlated with the proportion of CCR6(+)CXCR3(-)spike-specific circulating follicular helper T cells.