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mRNA 疫苗对原始和变异 SARS-CoV-2 株的保护活性。

Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains.

机构信息

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

出版信息

Sci Transl Med. 2022 Feb 2;14(630):eabm3302. doi: 10.1126/scitranslmed.abm3302.

DOI:10.1126/scitranslmed.abm3302
PMID:34846168
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8817234/
Abstract

Although mRNA vaccines encoding the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevent COVID-19, the emergence of new viral variants jeopardizes their efficacy. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike protein) or modified (mRNA-1273.351, designed for B.1.351 spike protein) Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Mice were immunized with either high-dose or low-dose formulations of the mRNA vaccines, where low-dose vaccination modeled suboptimal immune responses. Immunization with formulations at either dose induced neutralizing antibodies in serum against ancestral SARS-CoV-2 WA1/2020 and several virus variants, although serum titers were lower against the B.1.617.2 (Delta) virus. Protection against weight loss and lung pathology was observed with all high-dose vaccines against all viruses. However, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, showed breakthrough lung infections with B.1.617.2 and development of pneumonia in K18-hACE2 mice. Thus, in individuals with reduced immunity after mRNA vaccination, breakthrough infection and disease may occur with some SARS-CoV-2 variants.

摘要

尽管编码严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）刺突蛋白的 mRNA 疫苗可以预防 COVID-19，但新病毒变体的出现危及了它们的疗效。在这里，我们评估了历史（mRNA-1273，针对武汉-1 刺突蛋白设计）或改良（mRNA-1273.351，针对 B.1.351 刺突蛋白设计）的 Moderna mRNA 疫苗在 129S2 和 K18-hACE2 小鼠中的免疫原性和保护活性。小鼠用高剂量或低剂量的 mRNA 疫苗进行免疫接种，其中低剂量疫苗接种模拟了不完全的免疫反应。用两种剂量的疫苗进行免疫接种，均可诱导血清中针对原始 SARS-CoV-2 WA1/2020 和几种病毒变体的中和抗体，尽管针对 B.1.617.2（Delta）病毒的血清滴度较低。所有高剂量疫苗均能预防体重减轻和肺部病理变化，对所有病毒均有保护作用。然而，疫苗的低剂量制剂产生的抗体和 T 细胞反应幅度较低，导致 B.1.617.2 的突破性肺部感染，并在 K18-hACE2 小鼠中引发肺炎。因此，在接受 mRNA 疫苗接种后免疫力下降的个体中，一些 SARS-CoV-2 变体可能会导致突破性感染和疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93eb/9017966/446b7bd69681/scitranslmed.abm3302-f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93eb/9017966/446b7bd69681/scitranslmed.abm3302-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93eb/9017966/742c5de1016d/scitranslmed.abm3302-f1.jpg
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2
Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice.变异的 SARS-CoV-2 mRNA 疫苗在小鼠中作为初级或加强系列疫苗具有广泛的中和作用。
Vaccine. 2021 Dec 17;39(51):7394-7400. doi: 10.1016/j.vaccine.2021.11.001. Epub 2021 Nov 8.
3
Molecular basis of immune evasion by the Delta and Kappa SARS-CoV-2 variants.新冠病毒德尔塔和卡帕变种逃避免疫的分子基础
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）结合疫苗可引发强大的免疫反应，能够抵御不断演变的病毒变体。
Vaccine. 2025 Apr 30;54:126988. doi: 10.1016/j.vaccine.2025.126988. Epub 2025 Mar 6.
4
Developing mRNA Nanomedicines with Advanced Targeting Functions.开发具有先进靶向功能的信使核糖核酸纳米药物。
Nanomicro Lett. 2025 Feb 21;17(1):155. doi: 10.1007/s40820-025-01665-9.
5
Safety and Immunogenicity of the Live Attenuated Vaccine QazCOVID-Live Against Coronavirus Infection COVID-19: Pre-Clinical Study Results.减毒活疫苗QazCOVID-Live预防冠状病毒感染COVID-19的安全性和免疫原性：临床前研究结果
Vaccines (Basel). 2024 Dec 12;12(12):1401. doi: 10.3390/vaccines12121401.
6
Defining a highly conserved B cell epitope in the receptor binding motif of SARS-CoV-2 spike glycoprotein.确定严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突糖蛋白受体结合基序中的一个高度保守的B细胞表位。
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4
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5
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6
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7
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8
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Science. 2021 Sep 17;373(6561):1372-1377. doi: 10.1126/science.abj4176. Epub 2021 Aug 13.
9
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Cell. 2021 Aug 5;184(16):4220-4236.e13. doi: 10.1016/j.cell.2021.06.020. Epub 2021 Jun 17.