Single-cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine.

Single-cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine.
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DOI:
10.1172/jci.insight.153201
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发表时间:
2021-12-22
期刊:
影响因子:
8
通讯作者:
Messaoudi I
Messaoudi I
中科院分区:
医学1区
文献类型:
--
作者:
Sureshchandra S;Lewis SA;Doratt BM;Jankeel A;Coimbra Ibraim I;Messaoudi I

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SARS-CoV-2 mRNA 疫苗已显示出卓越的临床疗效,可为预防严重疾病提供强有力的保护。然而,我们对全面疫苗接种后转录和库变化的理解仍然不完整。我们使用 scRNA-Seq 和功能测定来比较 2 剂 mRNA 疫苗的体液和细胞反应与在无症状疾病恢复期个体中观察到的反应。我们的分析揭示了疫苗接种后刺突特异性 B 细胞、活化的 CD4+ T 细胞和强大的抗原特异性多功能 CD4+ T 细胞反应的富集。另一方面,尽管在疫苗接种和自然感染后都观察到克隆扩增的 CD8+ T 细胞,但 CD8+ T 细胞反应相对较弱且可变。此外,TCR 基因的使用是可变的,反映了人群中库的多样性和 MHC 多态性。自然感染诱导 CD8+ T 细胞克隆的扩增,与疫苗接种诱导的克隆相比,这些克隆占据不同的簇,并且可能识别 mRNA 疫苗中未见的病毒呈现的更广泛的病毒表位病毒抗原。我们的研究强调了协调的适应性免疫反应,其中早期 CD4+ T 细胞反应促进 B 细胞反应的发展和效应 CD8+ T 细胞的大幅扩增,共同能够促进未来的回忆反应。
mRNA vaccines for SARS-CoV-2 have shown exceptional clinical efficacy, providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used scRNA-Seq and functional assays to compare humoral and cellular responses to 2 doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4+ T cells, and robust antigen-specific polyfunctional CD4+ T cell responses following vaccination. On the other hand, although clonally expanded CD8+ T cells were observed following both vaccination and natural infection, CD8+ T cell responses were relatively weak and variable. In addition, TCR gene usage was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of CD8+ T cell clones that occupy distinct clusters compared to those induced by vaccination and likely recognize a broader set of viral antigens of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response in which early CD4+ T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8+ T cells, together capable of contributing to future recall responses.
DOI: 10.1038/s41586-021-03207-w
发表时间: 2021-03
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影响因子: 64.8
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发表时间: 2020-12-31
期刊: The New England journal of medicine
影响因子: --
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Polack FP;Thomas SJ;Kitchin N;Absalon J;Gurtman A;Lockhart S;Perez JL;Pérez Marc G;Moreira ED;Zerbini C;Bailey R;Swanson KA;Roychoudhury S;Koury K;Li P;Kalina WV;Cooper D;Frenck RW Jr;Hammitt LL;Türeci Ö;Nell H;Schaefer A;Ünal S;Tresnan DB;Mather S;Dormitzer PR;Şahin U;Jansen KU;Gruber WC;C4591001 Clinical Trial Group
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在老年受试者中,SARS-COV-2特异性CD8(+)T细胞的启动受损。
DOI: 10.3389/fimmu.2021.693054
发表时间: 2021
影响因子: 7.3
作者:
Gallerani E;Proietto D;Dallan B;Campagnaro M;Pacifico S;Albanese V;Marzola E;Marconi P;Caputo A;Appay V;Gavioli R;Nicoli F
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DOI: 10.1126/sciimmunol.abf7550
发表时间: 2021-04-14
期刊: Science immunology
影响因子: 24.8
作者:
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通讯作者: Hadrup SR
DOI: 10.1056/nejmoa2110345
发表时间: 2021-11-04
期刊: The New England journal of medicine
影响因子: --
作者:
Thomas SJ;Moreira ED Jr;Kitchin N;Absalon J;Gurtman A;Lockhart S;Perez JL;Pérez Marc G;Polack FP;Zerbini C;Bailey R;Swanson KA;Xu X;Roychoudhury S;Koury K;Bouguermouh S;Kalina WV;Cooper D;Frenck RW Jr;Hammitt LL;Türeci Ö;Nell H;Schaefer A;Ünal S;Yang Q;Liberator P;Tresnan DB;Mather S;Dormitzer PR;Şahin U;Gruber WC;Jansen KU;C4591001 Clinical Trial Group
通讯作者: C4591001 Clinical Trial Group