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展示RBD的腺病毒纳米颗粒在小鼠中诱导针对BA.5的保护性免疫反应。

Adenovirus Nanoparticles Displaying RBD Induce a Protective Immune Response Against BA.5 in Mice.

作者信息

Mo Chuncong, Wang Zhongfang, Liu Donglan, Yang Xiaoyun, Zhang Qiong, Ye Lihua, Yuan Shuai, Deng ShiDong, Lai Zhulan, Huang Deyi, Yang Yujie, Xu Duo, Yuan Jinwei, Zhu Yuhui, Liu Haoyi, Zhou Chengxing, Liao Xiaohong, Li Xiao, Liu Wenkuan, Zhou Rong, Tian Xingui

机构信息

State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center of Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong Province, 510182, People's Republic of China.

Guangzhou National Laboratory, Guangzhou, Guangdong Province, 510005, People's Republic of China.

出版信息

Int J Nanomedicine. 2025 Aug 6;20:9771-9785. doi: 10.2147/IJN.S511173. eCollection 2025.

DOI:10.2147/IJN.S511173
PMID:40791772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12336385/
Abstract

INTRODUCTION: Adenovirus (Ad) vectors demonstrated significant efficacy as vaccine vectors during the COVID-19 pandemic. Hexon is the major capsid protein, and multiple hypervariable regions (HVRs) have been used for displaying exogenous antigens and inducing a strong antibody responses. METHODS: We utilized SpyCatcher/SpyTag technology to incorporate SpyTag into HVR2, 4, and 7 of the hexon of the bivalent vaccine strain rAd3/7, respectively, to construct recombinant Ad, rAd3/7-SpyTag. The receptor-binding domain (RBD) of the SARS-CoV-2 BA5.2 strain fused with SpyCatcher was expressed as SpyCatcher-RBD, Spycatcher-RBD and rAd3/7-SpyTag were incubated in vitro to prepare a novel nanoparticle vaccine candidate, rAd3/7-SpyRBD, against SARS-CoV-2. Characterize rAd3/7-SpyRBD using Western blot, ELISA, transmission electron microscopy (TEM), and particle size measurement, and verify its immunogenicity through mouse immunization. RESULTS: We have successfully established a universal nanoparticle vaccine platform, rAd3/7-SpyTag, and the RBD protein was successfully displayed on the surface of rAd3/7-SpyTag. Compared with SpyCatcher-RBD, rAd3/7-SpyRBD can rapidly induce the production of antibodies and stronger immune responses. Both Spycatcher-RBD and rAd3/7-SpyRBD provide a protective immune response against BA.5 in mouse model mice and can be used as candidates for SARS-CoV-2 vaccine. We also found that rAd3/7-SpyRBD induced the production of neutralizing antibodies against Ad3 and Ad7, suggested that it could serve as an Ads vaccine candidate. CONCLUSION: We developed a universal nanoparticle vaccine platform and obtained a trivalent vaccine candidate rAd3/7-SpyRBD, against SARS-CoV-2, Ad3, and Ad7, and this is the first time to use SpyCatcher/SpyTag technology in a bivalent rAd3/7 vector for trivalent immunity.

摘要

引言：在新冠疫情期间，腺病毒（Ad）载体作为疫苗载体展现出显著功效。六邻体是主要的衣壳蛋白，多个高变区（HVRs）已被用于展示外源抗原并诱导强烈的抗体反应。 方法：我们利用SpyCatcher/SpyTag技术，分别将SpyTag整合到二价疫苗株rAd3/7六邻体的HVR2、4和7中，构建重组腺病毒rAd3/7-SpyTag。将与SpyCatcher融合的新冠病毒SARS-CoV-2 BA5.2株受体结合域（RBD）表达为SpyCatcher-RBD，在体外将SpyCatcher-RBD与rAd3/7-SpyTag孵育，制备一种针对SARS-CoV-2的新型纳米颗粒疫苗候选物rAd3/7-SpyRBD。使用蛋白质印迹法、酶联免疫吸附测定、透射电子显微镜（TEM）和粒度测量对rAd3/7-SpyRBD进行表征，并通过小鼠免疫验证其免疫原性。 结果：我们成功建立了一个通用的纳米颗粒疫苗平台rAd3/7-SpyTag，并且RBD蛋白成功展示在rAd3/7-SpyTag表面。与SpyCatcher-RBD相比，rAd3/7-SpyRBD能快速诱导抗体产生以及更强的免疫反应。SpyCatcher-RBD和rAd3/7-SpyRBD在小鼠模型中均能提供针对BA.5的保护性免疫反应，可作为SARS-CoV-2疫苗候选物。我们还发现rAd3/7-SpyRBD诱导产生了针对Ad3和Ad7的中和抗体，表明它可作为腺病毒疫苗候选物。 结论：我们开发了一个通用的纳米颗粒疫苗平台，并获得了一种针对SARS-CoV-2、Ad3和Ad7的三价疫苗候选物rAd3/7-SpyRBD，这是首次在二价rAd3/7载体中使用SpyCatcher/SpyTag技术实现三价免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/932415656f83/IJN-20-9771-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/8477cb531be8/IJN-20-9771-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/b0273d94dde3/IJN-20-9771-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/b22ab351b2ef/IJN-20-9771-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/c3fe004fb757/IJN-20-9771-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/58079f1923ba/IJN-20-9771-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/8b64cf24b11f/IJN-20-9771-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/932415656f83/IJN-20-9771-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/8477cb531be8/IJN-20-9771-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/b0273d94dde3/IJN-20-9771-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/b22ab351b2ef/IJN-20-9771-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/c3fe004fb757/IJN-20-9771-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/58079f1923ba/IJN-20-9771-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/8b64cf24b11f/IJN-20-9771-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f045/12336385/932415656f83/IJN-20-9771-g0007.jpg

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本文引用的文献

[1]
Mosaic RBD Nanoparticles Elicit Protective Immunity Against Multiple Human Coronaviruses in Animal Models.

Adv Sci (Weinh). 2024-3

[2]
SARS-CoV-2 convalescence and hybrid immunity elicits mucosal immune responses.

EBioMedicine. 2023-12

[3]
SpyTag/SpyCatcher display of influenza M2e peptide on norovirus-like particle provides stronger immunization than direct genetic fusion.

Front Cell Infect Microbiol. 2023

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Nat Rev Microbiol. 2023-2

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Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2.

Mol Ther. 2022-12-7

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Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models.

Science. 2022-8-5

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Emerg Microbes Infect. 2022-12

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A lethal mouse model for evaluating vaccine-associated enhanced respiratory disease during SARS-CoV-2 infection.

Sci Adv. 2022-1-7

[9]
Antigenicity and immunogenicity of HA2 and M2e influenza virus antigens conjugated to norovirus-like, VP1 capsid-based particles by the SpyTag/SpyCatcher technology.

Virology. 2022-1

[10]
Two-Component Nanoparticle Vaccine Displaying Glycosylated Spike S1 Domain Induces Neutralizing Antibody Response against SARS-CoV-2 Variants.

mBio. 2021-10-26

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