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靶向 RBD 的 COVID-19 mRNA 疫苗在非人灵长类动物中的长期稳定性和保护效力。

Long-term stability and protection efficacy of the RBD-targeting COVID-19 mRNA vaccine in nonhuman primates.

机构信息

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, 100071, Beijing, China.

Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun, 130122, China.

出版信息

Signal Transduct Target Ther. 2021 Dec 24;6(1):438. doi: 10.1038/s41392-021-00861-4.


DOI:10.1038/s41392-021-00861-4
PMID:34952914
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8703211/
Abstract

Messenger RNA (mRNA) vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic. Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use. Recently, we have developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor-binding domain (RBD) of SARS-CoV-2 (termed ARCoV), which confers complete protection in mouse model. Herein, we further characterized the protection efficacy of ARCoV in nonhuman primates and the long-term stability under normal refrigerator temperature. Intramuscular immunization of two doses of ARCoV elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques. More importantly, ARCoV vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2, and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of ARCoV. No evidence of antibody-dependent enhancement of infection was observed throughout the study. Finally, extensive stability assays showed that ARCoV can be stored at 2-8 °C for at least 6 months without decrease of immunogenicity. All these promising results strongly support the ongoing clinical trial.

摘要

信使 RNA(mRNA)疫苗技术在预防当前的 COVID-19 大流行方面显示出了其威力。两种针对 SARS-CoV-2 全长 S 蛋白的 mRNA 疫苗已被授权紧急使用。最近,我们开发了一种包裹 SARS-CoV-2 受体结合域(RBD)的脂质纳米颗粒包裹的 mRNA(称为 ARCoV),该疫苗在小鼠模型中提供了完全保护。在此,我们进一步在非人类灵长类动物中表征了 ARCoV 的保护效力,并在正常冰箱温度下评估了其长期稳定性。两剂 ARCoV 的肌内免疫在食蟹猴中引发了针对 SARS-CoV-2 的强大中和抗体和细胞反应。更重要的是,ARCoV 疫苗接种可显著保护猕猴免受 SARS-CoV-2 引起的急性肺部病变,并且所有用低或高剂量 ARCoV 免疫的动物的肺部病毒复制和鼻拭子分泌物均完全清除。整个研究过程中均未观察到抗体依赖性增强感染的证据。最后,广泛的稳定性研究表明,ARCoV 在 2-8°C 下至少可稳定保存 6 个月,而其免疫原性不会降低。所有这些有希望的结果都强烈支持正在进行的临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3f/8709864/f273df5927ac/41392_2021_861_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3f/8709864/8f3720feabc7/41392_2021_861_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3f/8709864/b5ec9d4f3d28/41392_2021_861_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3f/8709864/8b32aa7179ef/41392_2021_861_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3f/8709864/f273df5927ac/41392_2021_861_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3f/8709864/8f3720feabc7/41392_2021_861_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3f/8709864/b5ec9d4f3d28/41392_2021_861_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3f/8709864/8b32aa7179ef/41392_2021_861_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b3f/8709864/f273df5927ac/41392_2021_861_Fig4_HTML.jpg

相似文献

[1]
Long-term stability and protection efficacy of the RBD-targeting COVID-19 mRNA vaccine in nonhuman primates.

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本文引用的文献

[1]
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Cell. 2021-8-5

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Emerg Microbes Infect. 2021-12

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