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SARS-CoV-2 mRNA vaccination elicits robust and persistent T follicular helper cell response in humans
bioRxiv - Immunology Pub Date : 2021-09-08 , DOI: 10.1101/2021.09.08.459485
Philip A Mudd , Anastasia A Minervina , Mikhail V Pogorelyy , Jackson S Turner , Wooseob Kim , Elizaveta Kalaidina , Jan Petersen , Aaron J Schmitz , Tingting Lei , Alem Haile , Allison M Kirk , Robert C Mettelman , Jeremy Chase Crawford , Thi H.O Nguyen , Louise C Rowntree , Elisa Rosati , Michael K Klebert , Teresa Suessen , William D Middleton , Joshua Wolf , Sharlene A Teefey , Jane O'Halloran , Rachel M Presti , Katherine Kedzierska , Jamie Rossjohn , Paul Thomas , Ali Ellebedy ,

SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we show that frequency of TFH correlates with that of S-binding germinal center B cells. Mining of the responding TFH T cell receptor repertoire revealed a strikingly immunodominant HLADPB1* 04-restricted response to S167-180 in individuals with this allele, which is among the most common HLA alleles in humans. Paired blood and lymph node specimens show that while circulating S-specific TFH cells peak one week after the second immunization, S-specific TFH persist at nearly constant frequencies for at least six months. Collectively, our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine.

中文翻译:

SARS-CoV-2 mRNA 疫苗接种在人类中引发了强大而持久的 T 滤泡辅助细胞反应

SARS-CoV-2 mRNA 疫苗可诱导强大的抗尖峰 (S) 抗体和 CD4+ T 细胞反应。目前尚不清楚疫苗诱导的滤泡辅助 CD4+ T (TFH) 细胞反应是否有助于这种出色的免疫原性。使用细针抽吸从接受 BNT162b2 mRNA 疫苗的个体引流腋窝淋巴结,我们表明 TFH 的频率与 S 结合生发中心 B 细胞的频率相关。响应 TFH T 细胞受体库的挖掘揭示了具有该等位基因的个体对 S167-180 的显着免疫显性 HLADPB1* 04 限制性反应,这是人类中最常见的 HLA 等位基因之一。配对的血液和淋巴结标本显示,虽然循环 S 特异性 TFH 细胞在第二次免疫后一周达到峰值,S 特异性 TFH 以几乎恒定的频率持续至少六个月。总的来说,我们的结果强调了强大的 TFH 细胞反应在通过这种有效的人类疫苗建立长期免疫力方面发挥的关键作用。
更新日期:2021-09-12
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