研究揭示COVID-19康復患者的體液和循環濾泡輔助T細胞反應
作者：
小柯機器人發布時間：2020/7/16 15:56:51
澳大利亞墨爾本大學Adam K. Wheatley、Stephen J. Kent等研究人員合作報導了COVID-19康復患者的體液和循環濾泡輔助T細胞反應。該項研究成果於2020年7月13日在線發表在《自然—醫學》雜誌上。
研究人員表徵了2019冠狀病毒病康復患者（COVID-19）的體液和循環濾泡輔助性T細胞（cTFH）抵抗峰值的免疫力。研究人員發現，SARS-CoV-2感染後，突刺蛋白（S）特異性抗體、記憶B細胞和cTFH被一致地引發，這表明強大的體液免疫力並與血漿中和活性呈正相關。相對較低頻率的B細胞或對S受體結合域具有特異性的cTFH也被引發。
值得注意的是，S特異性cTFH的表型區分了具有有效中和反應的受試者，從而為進入臨床的S疫苗效力提供了潛在的生物標記。總體而言，儘管COVID-19恢復患者顯示出對S有效免疫識別的多個標誌，但觀察到的廣泛中和活性表明，疫苗可能需要策略來選擇性地靶向最有效的中和表位。
據悉，嚴重急性呼吸系統綜合症冠狀病毒2（SARS-CoV-2）的大流行極大地加快了全球疫苗研發的速度，其中大多數針對病毒的「突刺」糖蛋白（S）。S定位在病毒體表面，並介導細胞受體血管緊張素轉換酶2（ACE2）的識別。消除S-ACE2相互作用的中和抗體或間接阻止膜融合，是疫苗保護的工作方式。然而，儘管基於原型S的疫苗在動物模型中顯示出了希望，但是S在人類中的免疫原性仍難以分辨。
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