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Spike-specific circulating T follicular helper cell and cross-neutralizing antibody responses in COVID-19-convalescent individuals
Nature Microbiology ( IF 20.5 ) Pub Date : 2020-11-16 , DOI: 10.1038/s41564-020-00824-5
Jian Zhang 1 , Qian Wu 1 , Ziyan Liu 1 , Qijie Wang 2 , Jiajing Wu 3, 4 , Yabin Hu 1 , Tingting Bai 5 , Ting Xie 2 , Mincheng Huang 2 , Tiantian Wu 6 , Danhong Peng 2 , Weijin Huang 3 , Kun Jin 1 , Ling Niu 1 , Wangyuan Guo 1 , Dixian Luo 1 , Dongzhu Lei 1 , Zhijian Wu 1 , Guicheng Li 1 , Renbin Huang 1 , Yingbiao Lin 1 , Xiangping Xie 2 , Shuangyan He 2 , Yunfan Deng 7 , Jianghua Liu 8 , Weilang Li 9 , Zhongyi Lu 10 , Haifu Chen 11 , Ting Zeng 2 , Qingting Luo 12 , Yi-Ping Li 6 , Youchun Wang 3 , Wenpei Liu 1, 5, 13 , Xiaowang Qu 1, 14
Affiliation  

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1,2,3 and individuals with COVID-19 have symptoms that can be asymptomatic, mild, moderate or severe4,5. In the early phase of infection, T- and B-cell counts are substantially decreased6,7; however, IgM8,9,10,11 and IgG12,13,14 are detectable within 14 d after symptom onset. In COVID-19-convalescent individuals, spike-specific neutralizing antibodies are variable3,15,16. No specific drug or vaccine is available for COVID-19 at the time of writing; however, patients benefit from treatment with serum from COVID-19-convalescent individuals17,18. Nevertheless, antibody responses and cross-reactivity with other coronaviruses in COVID-19-convalescent individuals are largely unknown. Here, we show that the majority of COVID-19-convalescent individuals maintained SARS-CoV-2 spike S1- and S2-specific antibodies with neutralizing activity against the SARS-CoV-2 pseudotyped virus, and that some of the antibodies cross-neutralized SARS-CoV, Middle East respiratory syndrome coronavirus or both pseudotyped viruses. Convalescent individuals who experienced severe COVID-19 showed higher neutralizing antibody titres, a faster increase in lymphocyte counts and a higher frequency of CXCR3+ T follicular help (TFH) cells compared with COVID-19-convalescent individuals who experienced non-severe disease. Circulating TFH cells were spike specific and functional, and the frequencies of CXCR3+ TFH cells were positively associated with neutralizing antibody titres in COVID-19-convalescent individuals. No individuals had detectable autoantibodies. These findings provide insights into neutralizing antibody responses in COVID-19-convalescent individuals and facilitate the treatment and vaccine development for SARS-CoV-2 infection.



中文翻译:

COVID-19 恢复期个体的尖峰特异性循环 T 滤泡辅助细胞和交叉中和抗体反应

2019 年冠状病毒病 (COVID-19) 是由感染严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 1、2、3引起的,而 COVID-19 患者的症状可能是无症状、轻度、中度或重度4 ,5 . 在感染的早期阶段,T 细胞和 B 细胞计数显着减少6,7;然而,IgM 8,9,10,11和 IgG 12,13,14在症状出现后 14 天内可检测到。在 COVID-19 恢复期个体中,尖峰特异性中和抗体是可变的3,15,16。在撰写本文时,没有针对 COVID-19 的特定药物或疫苗;然而,患者受益于 COVID-19 恢复期个体的血清治疗17,18. 然而,在 COVID-19 恢复期个体中,抗体反应和与其他冠状病毒的交叉反应在很大程度上是未知的。在这里,我们表明大多数 COVID-19 恢复期个体保持 SARS-CoV-2 刺突 S1 和 S2 特异性抗体,对 SARS-CoV-2 假型病毒具有中和活性,并且一些抗体被交叉中和SARS-CoV、中东呼吸综合征冠状病毒或两种假型病毒。与经历非严重疾病的 COVID-19 恢复期个体相比,经历过严重 COVID-19 的恢复期个体显示出更高的中和抗体滴度、淋巴细胞计数增加更快和 CXCR3 + T 滤泡帮助 (T FH ) 细胞的频率更高。循环 T FH细胞具有尖峰特异性和功能性,CXCR3 + T FH细胞的频率与 COVID-19 恢复期个体的中和抗体滴度呈正相关。没有人有可检测到的自身抗体。这些发现为 COVID-19 恢复期个体的中和抗体反应提供了见解,并促进了 SARS-CoV-2 感染的治疗和疫苗开发。

更新日期:2020-11-16
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