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SARS-CoV-2 mRNA Vaccines: Immunological Mechanism and Beyond. ​

文献信息 ​

DOI10.3390/vaccines9020147
PMID33673048
期刊Vaccines
影响因子3.4
JCR 分区Q2
发表年份2021
被引次数156
关键词SARS-CoV-2, T滤泡辅助细胞, Th1细胞, 适应性免疫, 抗体
文献类型Journal Article, Review
ISSN2076-393X
期号9(2)
作者Emily Bettini, Michela Locci

一句话小结 ​

本研究综述了针对SARS-CoV-2的mRNA疫苗在动物模型和临床研究中的有效性，强调了其在诱导B细胞和T细胞适应性免疫反应方面的优势。研究结果表明，mRNA疫苗不仅能有效驱动免疫反应，还有助于提升疫苗研发的效率，对抗病原体感染具有重要意义。

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SARS-CoV-2 · T滤泡辅助细胞 · Th1细胞 · 适应性免疫 · 抗体

摘要 ​

要成功防护病原体感染，疫苗必须引发有效的适应性免疫反应，包括B细胞和T细胞的反应。尽管B细胞反应至关重要，因为它们可以介导抗体依赖的保护，但T细胞能够调节B细胞的活性，并直接参与清除感染病原体的细胞。在开发针对严重急性呼吸综合症冠状病毒2型（SARS-CoV-2）的有效疫苗的前所未有的竞赛中，信使RNA（mRNA）疫苗因其快速开发能力和驱动强大适应性免疫反应的能力而成为领先者。在这篇综述文章中，我们概述了在动物模型中的临床前研究结果以及评估SARS-CoV-2 mRNA疫苗有效性的临床研究，重点关注接种后适应性免疫反应。

英文摘要 ​

To successfully protect against pathogen infection, a vaccine must elicit efficient adaptive immunity, including B and T cell responses. While B cell responses are key, as they can mediate antibody-dependent protection, T cells can modulate B cell activity and directly contribute to the elimination of pathogen-infected cells. In the unprecedented race to develop an effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the respiratory disease coronavirus disease 2019 (COVID-19), messenger RNA (mRNA) vaccines have emerged as front runners thanks to their capacity for rapid development and ability to drive potent adaptive immune responses. In this review article, we provide an overview of the results from pre-clinical studies in animal models as well as clinical studies in humans that assessed the efficacy of SARS-CoV-2 mRNA vaccines, with a primary focus on adaptive immune responses post vaccination.

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主要研究问题 ​

  1. SARS-CoV-2 mRNA疫苗在不同人群中的免疫反应是否存在显著差异？
  2. 除了B细胞和T细胞，是否还有其他免疫细胞在mRNA疫苗的免疫机制中发挥重要作用？
  3. SARS-CoV-2 mRNA疫苗的长期免疫效果如何，与传统疫苗相比有什么不同？
  4. 在应对变异株方面，mRNA疫苗的适应性和有效性如何？
  5. 未来的疫苗研发中，mRNA技术可能会应用于哪些其他病原体的防治？

核心洞察 ​

研究背景和目的 ​

在2019年12月，SARS-CoV-2被确认为导致新冠肺炎（COVID-19）的病原体。到2020年底，该病已导致全球超过8000万感染和180万死亡，急需开发安全有效的疫苗。随着疫苗开发的加速，信使RNA（mRNA）疫苗因其快速开发能力和强大的适应性免疫反应而成为主要候选者。本综述旨在总结SARS-CoV-2 mRNA疫苗的免疫学机制，特别是疫苗接种后适应性免疫反应的现有知识。

主要方法/材料/实验设计 ​

本研究采用文献综述的方式，重点分析了多项临床和动物研究的数据，探讨了mRNA疫苗的设计策略、免疫反应及其效果。以下是技术路线的流程图：

Mermaid diagram

关键结果和发现 ​

  1. B细胞和抗体反应：mRNA疫苗能有效诱导抗SARS-CoV-2抗体的产生，研究显示单剂量30µg的mRNA疫苗在小鼠中能够在两周内产生高水平的特异性IgG抗体。
  2. T细胞反应：疫苗接种后，CD4 T细胞主要偏向Th1型，增强了对病毒的免疫应答，CD8 T细胞的激活也得到了证实。
  3. 临床试验结果：Moderna的mRNA-1273和BioNTech/Pfizer的BNT162b2疫苗在临床试验中均显示出超过90%的有效性，并且接种后产生了持久的中和抗体反应。

主要结论/意义/创新性 ​

mRNA疫苗展现出快速开发、强免疫反应和良好安全性的优势，成为应对SARS-CoV-2疫情的重要工具。这一平台的成功为未来疫苗开发和应对其他传染病提供了新的范式。

研究局限性和未来方向 ​

尽管mRNA疫苗显示出良好的免疫应答，但仍需关注以下问题：

  1. 过敏反应：个别接种者出现过敏反应，需进一步研究其机制。
  2. 免疫持久性：当前对疫苗诱导的免疫持续时间的了解仍有限，需要长期随访研究。
  3. 储存要求：mRNA疫苗需在低温条件下储存，这对分发和接种构成挑战。

未来的研究应着重于优化疫苗配方，评估不同人群（如老年人）的免疫反应，并探索新兴变种对疫苗效果的影响。

参考文献 ​

  1. Immune Responses Induced by mRNA Vaccination in Mice, Monkeys and Humans. - Alberto Cagigi;Karin Loré - Vaccines (2021)
  2. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. - Mark J Mulligan;Kirsten E Lyke;Nicholas Kitchin;Judith Absalon;Alejandra Gurtman;Stephen Lockhart;Kathleen Neuzil;Vanessa Raabe;Ruth Bailey;Kena A Swanson;Ping Li;Kenneth Koury;Warren Kalina;David Cooper;Camila Fontes-Garfias;Pei-Yong Shi;Özlem Türeci;Kristin R Tompkins;Edward E Walsh;Robert Frenck;Ann R Falsey;Philip R Dormitzer;William C Gruber;Uğur Şahin;Kathrin U Jansen - Nature (2020)
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引用本文的文献 ​

  1. Intervention Strategies for Seasonal and Emerging Respiratory Viruses with Drugs and Vaccines Targeting Viral Surface Glycoproteins. - Ralph A Tripp;John Stambas - Viruses (2021)
  2. An Updated Review of SARS-CoV-2 Vaccines and the Importance of Effective Vaccination Programs in Pandemic Times. - Cielo García-Montero;Oscar Fraile-Martínez;Coral Bravo;Diego Torres-Carranza;Lara Sanchez-Trujillo;Ana M Gómez-Lahoz;Luis G Guijarro;Natalio García-Honduvilla;Angel Asúnsolo;Julia Bujan;Jorge Monserrat;Encarnación Serrano;Melchor Álvarez-Mon;Juan A De León-Luis;Miguel A Álvarez-Mon;Miguel A Ortega - Vaccines (2021)
  3. Correlation between BNT162b2 mRNA Covid-19 vaccine-associated hypermetabolic lymphadenopathy and humoral immunity in patients with hematologic malignancy. - Dan Cohen;Shir Hazut Krauthammer;Yael C Cohen;Chava Perry;Irit Avivi;Yair Herishanu;Einat Even-Sapir - European journal of nuclear medicine and molecular imaging (2021)
  4. Rapid Development of Clinically Symptomatic Radiation Recall Pneumonitis Immediately Following COVID-19 Vaccination. - Cole R Steber;Janardhana Ponnatapura;Ryan T Hughes;Michael K Farris - Cureus (2021)
  5. Anti-SARS-CoV-2 Receptor-Binding Domain Total Antibodies Response in Seropositive and Seronegative Healthcare Workers Undergoing COVID-19 mRNA BNT162b2 Vaccination. - Gian Luca Salvagno;Brandon M Henry;Giovanni di Piazza;Laura Pighi;Simone De Nitto;Damiano Bragantini;Gian Luca Gianfilippi;Giuseppe Lippi - Diagnostics (Basel, Switzerland) (2021)
  6. mRNA Innovates the Vaccine Field. - Norbert Pardi - Vaccines (2021)
  7. Unveiling the Potential Role of Nanozymes in Combating the COVID-19 Outbreak. - Jafar Ali;Saira Naveed Elahi;Asghar Ali;Hassan Waseem;Rameesha Abid;Mohamed M Mohamed - Nanomaterials (Basel, Switzerland) (2021)
  8. Trigeminal and cervical radiculitis after tozinameran vaccination against COVID-19. - Kaavya Narasimhalu;Wai Ching Lee;Parag Ratnakar Salkade;Deidre Anne De Silva - BMJ case reports (2021)
  9. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. - Jackson S Turner;Jane A O'Halloran;Elizaveta Kalaidina;Wooseob Kim;Aaron J Schmitz;Julian Q Zhou;Tingting Lei;Mahima Thapa;Rita E Chen;James Brett Case;Fatima Amanat;Adriana M Rauseo;Alem Haile;Xuping Xie;Michael K Klebert;Teresa Suessen;William D Middleton;Pei-Yong Shi;Florian Krammer;Sharlene A Teefey;Michael S Diamond;Rachel M Presti;Ali H Ellebedy - Nature (2021)
  10. Addressing Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Following COVID-19 Vaccination: A Mini-Review of Practical Strategies. - Po-Wei Chen;Zong-Yun Tsai;Ting-Hsing Chao;Yi-Heng Li;Charles Jia-Yin Hou;Ping-Yen Liu - Acta Cardiologica Sinica (2021)

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