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研究揭示COVID-19康复患者的体液和循环滤泡辅助T细胞反应
2020-07-16 15:56

澳大利亚墨尔本大学Adam K. Wheatley、Stephen J. Kent等研究人员合作报道了COVID-19康复患者的体液和循环滤泡辅助T细胞反应。该项研究成果于2020年7月13日在线发表在《自然—医学》杂志上。

研究人员表征了2019冠状病毒病康复患者(COVID-19)的体液和循环滤泡辅助性T细胞(cTFH)抵抗峰值的免疫力。研究人员发现,SARS-CoV-2感染后,突刺蛋白(S)特异性抗体、记忆B细胞和cTFH被一致地引发,这表明强大的体液免疫力并与血浆中和活性呈正相关。相对较低频率的B细胞或对S受体结合域具有特异性的cTFH也被引发。
 
值得注意的是,S特异性cTFH的表型区分了具有有效中和反应的受试者,从而为进入临床的S疫苗效力提供了潜在的生物标记。总体而言,尽管COVID-19恢复患者显示出对S有效免疫识别的多个标志,但观察到的广泛中和活性表明,疫苗可能需要策略来选择性地靶向最有效的中和表位。
 
据悉,严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)的大流行极大地加快了全球疫苗研发的速度,其中大多数针对病毒的“突刺”糖蛋白(S)。S定位在病毒体表面,并介导细胞受体血管紧张素转换酶2(ACE2)的识别。消除S-ACE2相互作用的中和抗体或间接阻止膜融合,是疫苗保护的工作方式。然而,尽管基于原型S的疫苗在动物模型中显示出了希望,但是S在人类中的免疫原性仍难以分辨。
 
附:英文原文

Title: Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19

Author: Jennifer A. Juno, Hyon-Xhi Tan, Wen Shi Lee, Arnold Reynaldi, Hannah G. Kelly, Kathleen Wragg, Robyn Esterbauer, Helen E. Kent, C. Jane Batten, Francesca L. Mordant, Nicholas A. Gherardin, Phillip Pymm, Melanie H. Dietrich, Nichollas E. Scott, Wai-Hong Tham, Dale I. Godfrey, Kanta Subbarao, Miles P. Davenport, Stephen J. Kent, Adam K. Wheatley

Issue&Volume: 2020-07-13

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts1,2,3, most targeting the viral ‘spike’ glycoprotein (S). S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2)4,5,6. Eliciting neutralizing antibodies that block S–ACE2 interaction7,8,9, or indirectly prevent membrane fusion10, constitute an attractive modality for vaccine-elicited protection11. However, although prototypic S-based vaccines show promise in animal models12,13,14, 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.

DOI: 10.1038/s41591-020-0995-0

Source: https://www.nature.com/articles/s41591-020-0995-0

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:87.241
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章:《自然—医学》:Online/在线发表

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