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一种使用 SARS-CoV-2 刺突蛋白受体结合域的 SpyCatcher 多聚化的 COVID-19 疫苗候选物诱导产生了强烈的中和抗体反应。

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses.

机构信息

MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK.

Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK.

出版信息

Nat Commun. 2021 Jan 22;12(1):542. doi: 10.1038/s41467-020-20654-7.

DOI:10.1038/s41467-020-20654-7
PMID:33483491
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7822889/
Abstract

There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic.

摘要

需要有效的、负担得起的 SARS-CoV-2 疫苗来应对当前的大流行。在这项研究中，我们描述了一种针对 SARS-CoV-2 的蛋白质纳米颗粒疫苗。该疫苗基于冠状病毒刺突糖蛋白受体结合域（RBD）在合成病毒样颗粒（VLP）平台SpyCatcher003-mi3上的展示，使用 SpyTag/SpyCatcher 技术。在初免-加强方案中，低剂量的 RBD-SpyVLP 在小鼠和猪中诱导出强大的中和抗体反应，优于恢复期人类血清。我们使用 ACE2 阻断和假病毒或野生型 SARS-CoV-2 细胞感染的中和作用来评估抗体质量。使用单克隆抗体组的竞争测定，我们表明 RBD-SpyVLP 诱导出能够识别 RBD 关键表位的多克隆抗体反应，降低了选择中和逃逸突变体的可能性。此外，RBD-SpyVLP 具有热稳定性，可冻干而不失免疫原性，以促进全球分布并减少对冷链的依赖。这些数据表明，RBD-SpyVLP 具有很强的潜力，可以应对 COVID-19 大流行的临床和后勤挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/7822889/1ba7af1bf37a/41467_2020_20654_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/7822889/2ae027cff719/41467_2020_20654_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/7822889/f38757de7296/41467_2020_20654_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/7822889/146b9c086501/41467_2020_20654_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/7822889/c9c5d25fc481/41467_2020_20654_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/7822889/1ba7af1bf37a/41467_2020_20654_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/7822889/2ae027cff719/41467_2020_20654_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/7822889/f38757de7296/41467_2020_20654_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/7822889/146b9c086501/41467_2020_20654_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/7822889/c9c5d25fc481/41467_2020_20654_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/7822889/1ba7af1bf37a/41467_2020_20654_Fig5_HTML.jpg

相似文献

[1]
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[8]
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引用本文的文献

[1]
SARS-CoV-2 RBD Scaffolded by AP205 or TIP60 Nanoparticles and Delivered as mRNA Elicits Robust Neutralizing Antibody Responses.

Vaccines (Basel). 2025-7-22

[2]
A novel nanoparticle vaccine displaying multistage tuberculosis antigens confers protection in mice infected with H37Rv.

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[3]
Synthesis of Chirally Chimeric Protein Nanoparticle Vaccines via Mirror-Image Spy Chemistry.

Angew Chem Int Ed Engl. 2025-8-18

[4]
Computationally designed haemagglutinin with nanocage plug-and-display elicits pan-H5 influenza vaccine responses.

Emerg Microbes Infect. 2025-12

[5]
Mpox multiprotein virus-like nanoparticle vaccine induces neutralizing and protective antibodies in mice and non-human primates.

Nat Commun. 2025-5-21

[6]
Biophysics of SARS-CoV-2 spike protein's receptor-binding domain interaction with ACE2 and neutralizing antibodies: from computation to functional insights.

Biophys Rev. 2025-3-8

[7]
Protein nanocages: A new frontier in mucosal vaccine delivery and immune activation.

Hum Vaccin Immunother. 2025-12

[8]
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[9]
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[10]
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本文引用的文献

[1]
Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2.

Cell. 2020-10-31

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Nat Microbiol. 2020-10-26

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Sci Rep. 2020-10-23

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N Engl J Med. 2020-9-2

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Genome-wide analysis of SARS-CoV-2 virus strains circulating worldwide implicates heterogeneity.

Sci Rep. 2020-8-19

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Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19.

NPJ Vaccines. 2020-7-27

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