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嵌合刺突 mRNA 疫苗可预防小鼠感染 SARS-CoV 属病毒。

Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice.

机构信息

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

出版信息

Science. 2021 Aug 27;373(6558):991-998. doi: 10.1126/science.abi4506. Epub 2021 Jun 22.

DOI:10.1126/science.abi4506
PMID:34214046
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8899822/
Abstract

The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and SARS-CoV-2 in 2019 highlights the need to develop universal vaccination strategies against the broader subgenus. Using chimeric spike designs, we demonstrate protection against challenge from SARS-CoV, SARS-CoV-2, SARS-CoV-2 B.1.351, bat CoV (Bt-CoV) RsSHC014, and a heterologous Bt-CoV WIV-1 in vulnerable aged mice. Chimeric spike messenger RNAs (mRNAs) induced high levels of broadly protective neutralizing antibodies against high-risk Sarbecoviruses. By contrast, SARS-CoV-2 mRNA vaccination not only showed a marked reduction in neutralizing titers against heterologous Sarbecoviruses, but SARS-CoV and WIV-1 challenge in mice resulted in breakthrough infections. Chimeric spike mRNA vaccines efficiently neutralized D614G, mink cluster five, and the UK B.1.1.7 and South African B.1.351 variants of concern. Thus, multiplexed-chimeric spikes can prevent SARS-like zoonotic coronavirus infections with pandemic potential.

摘要

严重急性呼吸系统综合征冠状病毒（SARS-CoV）于 2003 年出现，而 SARS-CoV-2 则于 2019 年出现，这突显了需要针对更广泛的亚属开发通用疫苗接种策略。我们使用嵌合刺突设计，证明了对 SARS-CoV、SARS-CoV-2、SARS-CoV-2 B.1.351、蝙蝠 CoV（Bt-CoV）RsSHC014 和异种 Bt-CoV WIV-1 的挑战具有保护作用。脆弱的老年小鼠。嵌合刺突信使 RNA（mRNA）诱导了针对高风险 Sarbecoviruses 的高水平广泛保护中和抗体。相比之下，SARS-CoV-2 mRNA 疫苗不仅对异源 Sarbecoviruses 的中和滴度明显降低，而且 SARS-CoV 和 WIV-1 在小鼠中的挑战导致突破性感染。嵌合刺突 mRNA 疫苗可有效中和 D614G、水貂 5 群以及英国 B.1.1.7 和南非 B.1.351 关注变体。因此，多重嵌合刺突可预防具有大流行潜力的类似 SARS 的人畜共患冠状病毒感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/0cfc384f3aef/science.abi4506-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/d1ecf7901a2f/keyimage.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/33d881a24f2c/science.abi4506-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/6f4a30ae9363/science.abi4506-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/1a996cc24f7a/science.abi4506-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/0a93eb568a91/science.abi4506-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/0cfc384f3aef/science.abi4506-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/d1ecf7901a2f/keyimage.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/33d881a24f2c/science.abi4506-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/6f4a30ae9363/science.abi4506-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/1a996cc24f7a/science.abi4506-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/0a93eb568a91/science.abi4506-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d9/10026980/0cfc384f3aef/science.abi4506-f5.jpg

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引用本文的文献

[1]
Challenges to the Effectiveness and Immunogenicity of COVID-19 Vaccines: A Narrative Review with a Systematic Approach.

Vaccines (Basel). 2025-7-24

[2]
A novel and safe SmartCap SC101 to develop the COVID-19 mRNA vaccine STP2104 inducing potent immune responses in humans.

Front Immunol. 2025-6-16

[3]
Phylogeny-driven design of broadly protective sarbecovirus receptor-binding domain nanoparticle vaccines.

bioRxiv. 2025-5-13

[4]
From genetic code to global health: the impact of nucleic acid vaccines on disease prevention and treatment.

RSC Med Chem. 2025-4-24

[5]
Beyond COVID-19: the promise of next-generation coronavirus vaccines.

Npj Viruses. 2024-8-22

[6]
Immunological drivers of zoonotic virus emergence, evolution, and endemicity.

Immunity. 2025-4-8

[7]
Targeted delivery of TGF-β mRNA to murine lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers.

Nat Commun. 2025-2-21

[8]
Structural characterization of influenza group 1 chimeric hemagglutinins as broad vaccine immunogens.

Proc Natl Acad Sci U S A. 2025-2-18

[9]
Structural prediction of chimeric immunogen candidates to elicit targeted antibodies against betacoronaviruses.

PLoS Comput Biol. 2025-2-5

[10]
An Evaluation of the Cellular and Humoral Response of a Multi-Epitope Vaccine Candidate Against COVID-19 with Different Alum Adjuvants.

Pathogens. 2024-12-9

本文引用的文献

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