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mRNA 疫苗的免疫原性机制及其在促进 SARS-CoV-2 适应性保护方面的局限性。

Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2.

机构信息

Department of Medical Microbiology & Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bahru, Kelantan, Malaysia.

School of Health Sciences, Universiti Sains Malaysia, Kota Bahru, Kelantan, Malaysia.

出版信息

PeerJ. 2022 Mar 9;10:e13083. doi: 10.7717/peerj.13083. eCollection 2022.

DOI:10.7717/peerj.13083
PMID:35287350
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8917804/
Abstract

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) in late 2019, hundreds of millions of people have been infected worldwide. There have been unprecedented efforts in acquiring effective vaccines to confer protection against the disease. mRNA vaccines have emerged as promising alternatives to conventional vaccines due to their high potency with the capacity for rapid development and low manufacturing costs. In this review, we summarize the currently available vaccines against SARS-CoV-2 in development, with the focus on the concepts of mRNA vaccines, their antigen selection, delivery and optimization to increase the immunostimulatory capability of mRNA as well as its stability and translatability. We also discuss the host immune responses to the SARS-CoV-2 infection and expound in detail, the adaptive immune response upon immunization with mRNA vaccines, in which high levels of spike-specific IgG and neutralizing antibodies were detected after two-dose vaccination. mRNA vaccines have been shown to induce a robust CD8T cell response, with a balanced CD4 T1/T2 response. We further discuss the challenges and limitations of COVID-19 mRNA vaccines, where newly emerging variants of SARS-CoV-2 may render currently deployed vaccines less effective. Imbalanced and inappropriate inflammatory responses, resulting from hyper-activation of pro-inflammatory cytokines, which may lead to vaccine-associated enhanced respiratory disease (VAERD) and rare cases of myocarditis and pericarditis also are discussed.

摘要

自 2019 年底严重急性呼吸综合征冠状病毒 2(SARS-CoV-2),即 2019 年冠状病毒病(COVID-19)的病原体出现以来,全球已有数亿人感染。为了获得针对这种疾病的有效疫苗,人们进行了前所未有的努力。由于 mRNA 疫苗具有高效、快速开发和低成本制造的能力,因此已成为传统疫苗的有前途的替代品。在这篇综述中,我们总结了目前正在开发的针对 SARS-CoV-2 的疫苗,重点介绍了 mRNA 疫苗的概念、其抗原选择、递送和优化,以提高 mRNA 的免疫刺激性及其稳定性和可翻译性。我们还讨论了宿主对 SARS-CoV-2 感染的免疫反应,并详细阐述了接种 mRNA 疫苗后的适应性免疫反应,其中在两剂接种后检测到高水平的刺突特异性 IgG 和中和抗体。mRNA 疫苗已被证明能诱导强烈的 CD8T 细胞反应,并能平衡 CD4T1/T2 反应。我们进一步讨论了 COVID-19 mRNA 疫苗的挑战和局限性,其中 SARS-CoV-2 的新出现变体可能会使目前部署的疫苗效果降低。还讨论了不平衡和不适当的炎症反应,这是由于促炎细胞因子的过度激活所致,这可能导致与疫苗相关的加重性呼吸道疾病(VAERD)和罕见的心肌炎和心包炎病例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/866a/8917804/736ce7c48a84/peerj-10-13083-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/866a/8917804/c24652cb72ac/peerj-10-13083-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/866a/8917804/8d7f861d3e08/peerj-10-13083-g002.jpg
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