SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses.
SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses.
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DOI：
10.1038/s41586-021-03738-2
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发表时间：
2021-08
期刊：
影响因子：
64.8
通讯作者：
Ellebedy AH
中科院分区：
文献类型：
--
作者：
Turner JS;O'Halloran JA;Kalaidina E;Kim W;Schmitz AJ;Zhou JQ;Lei T;Thapa M;Chen RE;Case JB;Amanat F;Rauseo AM;Haile A;Xie X;Klebert MK;Suessen T;Middleton WD;Shi PY;Krammer F;Teefey SA;Diamond MS;Presti RM;Ellebedy AH
基于SARS-CoV-2 mRNA的疫苗预防COVID-19的有效性约为95%。这些疫苗在人体中诱导的分泌抗体的浆母细胞和生发中心B细胞的动力学尚不清楚。在这里，我们检测了14名接受2剂BNT 162 b2（一种编码全长SARS-CoV-2刺突（S）基因的mRNA疫苗）的个体的外周血（n = 41）和引流淋巴结中的抗原特异性B细胞反应。循环中分泌IgG和IgA的浆母细胞靶向S蛋白在第二次免疫后一周达到峰值，然后下降，三周后检测不到。这些浆母细胞反应先于最高水平的血清抗S结合和中和抗体，以早期循环的SARS-CoV-2菌株以及新出现的变体，特别是在以前感染过SARS-CoV-2的个体中（产生最强烈的血清学反应）。通过检查细针抽吸引流腋窝淋巴结，我们确定了生发中心B细胞，结合S蛋白在所有参与者谁是采样后，初级免疫。高频率的S-结合生发中心B细胞和浆母细胞持续在这些引流淋巴结至少12周后加强免疫。来源于生发中心B细胞的S结合单克隆抗体主要靶向S蛋白的受体结合结构域，较少的克隆结合到N-末端结构域或与人β冠状病毒OC 43和HKU 1的S蛋白共有的表位。这些后者的交叉反应性B细胞克隆具有更高水平的体细胞超突变相比，仅识别SARS-CoV-2 S蛋白，这表明记忆B细胞起源。我们的研究表明，基于SARS-CoV-2 mRNA的人类疫苗接种诱导了持久的生发中心B细胞应答，这使得能够产生强大的体液免疫。
SARS-CoV-2 mRNA-based vaccines are about 95% effective in preventing COVID-19. The dynamics of antibody-secreting plasmablasts and germinal centre B cells induced by these vaccines in humans remain unclear. Here we examined antigen-specific B cell responses in peripheral blood (n = 41) and draining lymph nodes in 14 individuals who had received 2 doses of BNT162b2, an mRNA-based vaccine that encodes the full-length SARS-CoV-2 spike (S) gene. Circulating IgG- and IgA-secreting plasmablasts that target the S protein peaked one week after the second immunization and then declined, becoming undetectable three weeks later. These plasmablast responses preceded maximal levels of serum anti-S binding and neutralizing antibodies to an early circulating SARS-CoV-2 strain as well as emerging variants, especially in individuals who had previously been infected with SARS-CoV-2 (who produced the most robust serological responses). By examining fine needle aspirates of draining axillary lymph nodes, we identified germinal centre B cells that bound S protein in all participants who were sampled after primary immunization. High frequencies of S-binding germinal centre B cells and plasmablasts were sustained in these draining lymph nodes for at least 12 weeks after the booster immunization. S-binding monoclonal antibodies derived from germinal centre B cells predominantly targeted the receptor-binding domain of the S protein, and fewer clones bound to the N-terminal domain or to epitopes shared with the S proteins of the human betacoronaviruses OC43 and HKU1. These latter cross-reactive B cell clones had higher levels of somatic hypermutation as compared to those that recognized only the SARS-CoV-2 S protein, which suggests a memory B cell origin. Our studies demonstrate that SARS-CoV-2 mRNA-based vaccination of humans induces a persistent germinal centre B cell response, which enables the generation of robust humoral immunity.
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影响因子：
12.4
作者：
Kariko, Katalin;Muramatsu, Hiromi;Welsh, Frank A.;Ludwig, Janos;Kato, Hiroki;Akira, Shizuo;Weissman, Drew
通讯作者：
Weissman, Drew
DOI：
10.1073/pnas.1402485111
发表时间：
2014-07-01
影响因子：
11.1
作者：
Good-Jacobson, Kim L.;Chen, Yunshun;Tarlinton, David
通讯作者：
Tarlinton, David
DOI：
10.1073/pnas.1417683112
发表时间：
2015-02-24
影响因子：
11.1
作者：
Gadala-Maria, Daniel;Yaari, Gur;Kleinstein, Steven H.
通讯作者：
Kleinstein, Steven H.
影响因子：
30.5
作者：
Dogan, Ismail;Bertocci, Barbara;Weill, Jean-Claude
通讯作者：
Weill, Jean-Claude
影响因子：
30.3
作者：
Case, James Brett;Rothlauf, Paul W.;Whelan, Sean P. J.
通讯作者：
Whelan, Sean P. J.