SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation.
SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation.
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SARS-COV-2 mRNA疫苗促进与中和抗体产生相关的有效抗原特异性生发中心反应。
DOI：
10.1016/j.immuni.2020.11.009
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发表时间：
2020-12-15
期刊：
影响因子：
32.4
通讯作者：
Locci M
中科院分区：
文献类型：
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作者：
Lederer K;Castaño D;Gómez Atria D;Oguin TH 3rd;Wang S;Manzoni TB;Muramatsu H;Hogan MJ;Amanat F;Cherubin P;Lundgreen KA;Tam YK;Fan SHY;Eisenlohr LC;Maillard I;Weissman D;Bates P;Krammer F;Sempowski GD;Pardi N;Locci M
部署针对严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）的有效疫苗对于消除2019冠状病毒病（COVID-19）大流行至关重要。许多许可的疫苗通过诱导长寿命浆细胞（LLPC）和记忆B细胞（MBC）来提供保护，这些细胞类型通常在生发中心（GC）反应期间产生。在这里，我们直接比较了两种疫苗平台-mRNA疫苗和用MF 59样佐剂配制的重组蛋白-寻找它们随着时间的推移定量和定性塑造SARS-CoV-2特异性初级GC反应的能力。我们证明了用SARS-CoV-2 mRNA单次免疫，而不是用重组蛋白疫苗，引起了有效的SARS-CoV-2特异性GC B和T滤泡辅助细胞（Tfh）反应以及LLPC和MBC。重要的是，GC反应与中和抗体产生强烈相关。mRNA疫苗更有效地诱导Tfh细胞程序的关键调节因子，并影响Tfh细胞的功能特性。总之，这项研究确定SARS-CoV-2 mRNA疫苗作为促进强大的GC衍生免疫应答的强有力的候选者。SARS-CoV-2 mRNA疫苗引发有效的GC B细胞应答GC应答与中和抗体的稳健发展相关SARS-CoV-2 mRNA疫苗促进抗原特异性Tfh细胞Tfh细胞程序的关键元件由SARS-CoV-2 mRNA疫苗调节。显示SARS-CoV-2的基于核酸的疫苗平台，其有效地诱导生发中心（GC）应答。GC是形成高质量保护性抗体反应的微解剖学位点。该等疫苗平台可能是缓解COVID-19大流行的有希望的候选者。
The deployment of effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to eradicate the coronavirus disease 2019 (COVID-19) pandemic. Many licensed vaccines confer protection by inducing long-lived plasma cells (LLPCs) and memory B cells (MBCs), cell types canonically generated during germinal center (GC) reactions. Here, we directly compared two vaccine platforms—mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant—looking for their abilities to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time. We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPCs and MBCs. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells. Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses. SARS-CoV-2 mRNA vaccines elicit potent GC B cell responses GC responses are associated with a robust development of neutralizing antibodies SARS-CoV-2 mRNA vaccines promote antigen-specific Tfh cells Key elements of the Tfh cell program are modulated by SARS-CoV-2 mRNA vaccines Herein, Lederer et al. show a nucleic-acid-based vaccine platform for SARS-CoV-2 that potently induces germinal center (GC) responses. GCs are microanatomical sites harboring the formation of high-quality, protective antibody responses. Such vaccine platforms can be promising candidates to mitigate the COVID-19 pandemic.
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影响因子：
7.3
作者：
Lindgren, Gustaf;Ols, Sebastian;Lore, Karin
通讯作者：
Lore, Karin
影响因子：
158.5
作者：
Keech, Cheryl;Albert, Gary;Glenn, Gregory M.
通讯作者：
Glenn, Gregory M.
影响因子：
82.9
作者：
Amanat F;Stadlbauer D;Strohmeier S;Nguyen THO;Chromikova V;McMahon M;Jiang K;Arunkumar GA;Jurczyszak D;Polanco J;Bermudez-Gonzalez M;Kleiner G;Aydillo T;Miorin L;Fierer DS;Lugo LA;Kojic EM;Stoever J;Liu STH;Cunningham-Rundles C;Felgner PL;Moran T;García-Sastre A;Caplivski D;Cheng AC;Kedzierska K;Vapalahti O;Hepojoki JM;Simon V;Krammer F
通讯作者：
Krammer F
影响因子：
32.4
作者：
Mesin, Luka;Ersching, Jonatan;Victora, Gabriel D.
通讯作者：
Victora, Gabriel D.
DOI：
10.1038/nri3804
发表时间：
2015-03
期刊：
Nature reviews. Immunology
影响因子：
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作者：
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