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mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern.

文献信息

DOI10.1126/science.abm0829
PMID34648302
期刊Science (New York, N.Y.)
影响因子45.8
JCR 分区Q1
发表年份2021
被引次数558
关键词mRNA疫苗, 免疫记忆, SARS-CoV-2, 变异株, T细胞
文献类型Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
ISSN0036-8075
页码abm0829
期号374(6572)
作者Rishi R Goel, Mark M Painter, Sokratis A Apostolidis, Divij Mathew, Wenzhao Meng, Aaron M Rosenfeld, Kendall A Lundgreen, Arnold Reynaldi, David S Khoury, Ajinkya Pattekar, Sigrid Gouma, Leticia Kuri-Cervantes, Philip Hicks, Sarah Dysinger, Amanda Hicks, Harsh Sharma, Sarah Herring, Scott Korte, Amy E Baxter, Derek A Oldridge, Josephine R Giles, Madison E Weirick, Christopher M McAllister, Moses Awofolaju, Nicole Tanenbaum, Elizabeth M Drapeau, Jeanette Dougherty, Sherea Long, Kurt D'Andrea, Jacob T Hamilton, Maura McLaughlin, Justine C Williams, Sharon Adamski, Oliva Kuthuru, Ian Frank, Michael R Betts, Laura A Vella, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Scott E Hensley, Miles P Davenport, Paul Bates, Eline T Luning Prak, Allison R Greenplate, E John Wherry

一句话小结

本研究分析了SARS-CoV-2 mRNA疫苗接种后未感染和已康复个体的免疫反应,发现尽管抗体水平在接种后6个月内有所下降,但大多数受试者仍能检测到抗体,并且功能性记忆B细胞和特异性T细胞的数量在此期间增加。此研究为理解mRNA疫苗接种后的免疫记忆的持久性提供了重要依据,强调了其对抗SARS-CoV-2及变种的长期保护潜力。

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mRNA疫苗 · 免疫记忆 · SARS-CoV-2 · 变异株 · T细胞

摘要

针对严重急性呼吸综合症冠状病毒2型(SARS-CoV-2)信使RNA(mRNA)疫苗接种后免疫记忆的持久性仍不明确。在本研究中,我们对SARS-CoV-2未感染和已康复个体在接种后6个月内的疫苗反应进行了纵向分析。抗体水平从峰值下降,但在大多数受试者中在6个月时仍然可检测到。相比之下,mRNA疫苗产生了功能性记忆B细胞,这些细胞的数量在接种后3到6个月间增加,其中大多数细胞能够交叉结合Alpha、Beta和Delta变种。mRNA疫苗接种还诱导了抗原特异性的CD4+和CD8+ T细胞,并且早期的CD4+ T细胞反应与长期的体液免疫相关。对于具有先前免疫的个体,接种后的记忆反应主要增加了抗体水平,而没有显著改变抗体衰减速率。总体而言,这些发现表明,在mRNA疫苗接种后,针对SARS-CoV-2及其变种的细胞免疫记忆至少持续6个月。

英文摘要

The durability of immune memory after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination remains unclear. In this study, we longitudinally profiled vaccine responses in SARS-CoV-2–naïve and –recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. By contrast, mRNA vaccines generated functional memory B cells that increased from 3 to 6 months postvaccination, with the majority of these cells cross-binding the Alpha, Beta, and Delta variants. mRNA vaccination further induced antigen-specific CD4+ and CD8+ T cells, and early CD4+ T cell responses correlated with long-term humoral immunity. Recall responses to vaccination in individuals with preexisting immunity primarily increased antibody levels without substantially altering antibody decay rates. Together, these findings demonstrate robust cellular immune memory to SARS-CoV-2 and its variants for at least 6 months after mRNA vaccination.

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主要研究问题

  1. mRNA疫苗在对抗其他病毒时的免疫记忆表现如何?
  2. 除了mRNA疫苗,还有哪些类型的疫苗能有效诱导对SARS-CoV-2的免疫记忆?
  3. 针对不同人群(如老年人、免疫缺陷者)mRNA疫苗的免疫记忆效果是否存在差异?
  4. 如何评估mRNA疫苗诱导的细胞免疫记忆在未来疫情中的实际应用价值?
  5. mRNA疫苗在变异株的应对能力上与传统疫苗相比有何优势和劣势?

核心洞察

研究背景和目的

新冠疫情导致全球重大健康危机,疫苗接种被认为是控制疫情的重要手段。mRNA疫苗(如Pfizer-BioNTech和Moderna)已被广泛使用,显示出高效的保护效果。本文旨在探讨mRNA疫苗接种后对SARS-CoV-2及其变异株的免疫记忆的持久性,特别关注抗体、记忆B细胞和T细胞的动态变化。

主要方法/材料/实验设计

本研究采用纵向观察设计,收集61名接种者的348个样本,分为SARS-CoV-2感染过的(16人)和未感染过的(45人)两组。样本在接种前、接种后1周、3个月和6个月时收集。研究主要测量抗体反应、记忆B细胞和T细胞的变化。采用流式细胞术、酶联免疫吸附试验(ELISA)和伪病毒中和实验等方法进行免疫分析。

Mermaid diagram

关键结果和发现

  1. 抗体反应:接种后抗体水平在1周达到峰值,随后逐渐下降,但在6个月时大多数个体仍可检测到抗体。
  2. 记忆B细胞:在接种后3-6个月,记忆B细胞频率持续增加,尤其是在未感染者中,显示出持久的免疫记忆。
  3. T细胞反应:CD4+ T细胞和CD8+ T细胞的反应在接种后显著增强,但CD8+ T细胞的持久性较低,6个月后大多数个体的T细胞反应有所下降。

主要结论/意义/创新性

研究表明,mRNA疫苗能够有效诱导持久的免疫记忆,尤其是记忆B细胞在接种后6个月仍能显著增加并对变异株具有交叉反应能力。这些发现为疫苗接种策略提供了重要的理论基础,尤其是在面对新出现的变异株时,强调了加强免疫的必要性。

研究局限性和未来方向

尽管本研究提供了重要数据,但样本量相对较小,且参与者主要为年轻健康个体,可能不完全代表老年人或有基础疾病人群的免疫反应。此外,未来研究应关注不同时间点的免疫动态变化,以及在不同人群中疫苗的长期效果。还需探索加强针接种对免疫记忆的影响,以及对新变异株的保护作用。

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  1. mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants. - Aurélien Sokal;Giovanna Barba-Spaeth;Ignacio Fernández;Matteo Broketa;Imane Azzaoui;Andréa de La Selle;Alexis Vandenberghe;Slim Fourati;Anais Roeser;Annalisa Meola;Magali Bouvier-Alias;Etienne Crickx;Laetitia Languille;Marc Michel;Bertrand Godeau;Sébastien Gallien;Giovanna Melica;Yann Nguyen;Virginie Zarrouk;Florence Canoui-Poitrine;France Pirenne;Jérôme Mégret;Jean-Michel Pawlotsky;Simon Fillatreau;Pierre Bruhns;Felix A Rey;Jean-Claude Weill;Claude-Agnès Reynaud;Pascal Chappert;Matthieu Mahévas - Immunity (2021)
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