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mRNA疫苗对原始株和变异株严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的保护活性。

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

作者信息

Ying Baoling, Whitener Bradley, VanBlargan Laura A, Hassan Ahmed O, Shrihari Swathi, Liang Chieh-Yu, Karl Courtney E, Mackin Samantha, Chen Rita E, Kafai Natasha M, Wilks Samuel H, Smith Derek J, Carreño Juan Manuel, Singh Gagandeep, Krammer Florian, Carfi Andrea, Elbashir Sayda, Edwards Darin K, Thackray Larissa B, Diamond Michael S

机构信息

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

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

出版信息

bioRxiv. 2021 Aug 26:2021.08.25.457693. doi: 10.1101/2021.08.25.457693.

DOI:10.1101/2021.08.25.457693
PMID:34462745
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8404887/
Abstract

Although mRNA vaccines prevent COVID-19, variants jeopardize their efficacy as immunity wanes. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike) or modified (mRNA-1273.351, designed for B.1.351 spike) preclinical Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Immunization with high or low dose formulations of mRNA vaccines induced neutralizing antibodies in serum against ancestral SARS-CoV-2 and several variants, although levels were lower particularly 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. Nonetheless, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, and serve as a possible model for waning immunity, showed breakthrough lung infection and pneumonia with B.1.617.2. Thus, as levels of immunity induced by mRNA vaccines decline, breakthrough infection and disease likely will occur with some SARS-CoV-2 variants, suggesting a need for additional booster regimens.

摘要

尽管mRNA疫苗可预防新冠病毒病，但随着免疫力下降，病毒变种会危及疫苗的效力。在此，我们评估了历史版本（为武汉-1毒株刺突蛋白设计的mRNA-1273）或改良版本（为B.1.351毒株刺突蛋白设计的mRNA-1273.351）的临床前Moderna mRNA疫苗在129S2和K18-hACE2小鼠中的免疫原性和保护活性。用高剂量或低剂量配方的mRNA疫苗免疫可诱导血清中产生针对原始严重急性呼吸综合征冠状病毒2（SARS-CoV-2）及其几种变种的中和抗体，不过特别是针对B.1.617.2（德尔塔）病毒的抗体水平较低。所有高剂量疫苗对所有病毒均显示出预防体重减轻和肺部病理变化的作用。尽管如此，低剂量配方疫苗产生的抗体和T细胞反应强度较低，可作为免疫力下降的一种可能模型，该配方疫苗对B.1.617.2病毒出现了突破性肺部感染和肺炎。因此，随着mRNA疫苗诱导的免疫力水平下降，一些SARS-CoV-2变种可能会导致突破性感染和疾病，这表明需要额外的加强免疫方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/b33f0389def1/nihpp-2021.08.25.457693v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/c9b215264705/nihpp-2021.08.25.457693v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/37e19d1d8eac/nihpp-2021.08.25.457693v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/4a829a8d1478/nihpp-2021.08.25.457693v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/a4cf5d51786d/nihpp-2021.08.25.457693v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/17333b7a53e1/nihpp-2021.08.25.457693v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/37b10390fada/nihpp-2021.08.25.457693v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/b33f0389def1/nihpp-2021.08.25.457693v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/c9b215264705/nihpp-2021.08.25.457693v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/37e19d1d8eac/nihpp-2021.08.25.457693v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/4a829a8d1478/nihpp-2021.08.25.457693v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/a4cf5d51786d/nihpp-2021.08.25.457693v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/17333b7a53e1/nihpp-2021.08.25.457693v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/37b10390fada/nihpp-2021.08.25.457693v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c50e/8404887/b33f0389def1/nihpp-2021.08.25.457693v1-f0007.jpg

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