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展示针对H3N2流感病毒感染的双抗原簇的T4噬菌体

T4 Phage Displaying Dual Antigen Clusters Against H3N2 Influenza Virus Infection.

作者信息

Liu Shenglong, Lin Mengzhou, Zhou Xin

机构信息

College of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou 225009, China.

Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.

出版信息

Vaccines (Basel). 2025 Jan 13;13(1):70. doi: 10.3390/vaccines13010070.


DOI:10.3390/vaccines13010070
PMID:39852849
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11769387/
Abstract

BACKGROUND: The current H3N2 influenza subunit vaccine exhibits weak immunogenicity, which limits its effectiveness in preventing and controlling influenza virus infections. METHODS: In this study, we aimed to develop a T4 phage-based nanovaccine designed to enhance the immunogenicity of two antigens by displaying the HA1 and M2e antigens of the H3N2 influenza virus on each phage nanoparticle. Specifically, we fused the Soc protein with the HA1 antigen and the Hoc protein with the M2e antigen, assembling them onto a T4 phage that lacks Soc and Hoc proteins (SocHocT4), thereby constructing a nanovaccine that concurrently presents both HA1 and M2e antigens. RESULTS: The analysis of the optical density of the target protein bands indicated that each particle could display approximately 179 HA1 and 68 M2e antigen molecules. Additionally, animal experiments demonstrated that this nanoparticle vaccine displaying dual antigen clusters induced a stronger specific immune response, higher antibody titers, a more balanced Th1/Th2 immune response, and enhanced CD4 and CD8 T cell effects compared to immunization with HA1 and M2e antigen molecules alone. Importantly, mice immunized with the T4 phage displaying dual antigen clusters achieved full protection (100% protection) against the H3N2 influenza virus, highlighting its robust protective efficacy. CONCLUSIONS: In summary, our findings indicate that particles based on a T4 phage displaying antigen clusters exhibit ideal immunogenicity and protective effects, providing a promising strategy for the development of subunit vaccines against various viruses beyond influenza.

摘要

背景:目前的H3N2流感亚单位疫苗免疫原性较弱,这限制了其在预防和控制流感病毒感染方面的有效性。 方法:在本研究中,我们旨在开发一种基于T4噬菌体的纳米疫苗,通过在每个噬菌体纳米颗粒上展示H3N2流感病毒的HA1和M2e抗原,增强两种抗原的免疫原性。具体而言,我们将Soc蛋白与HA1抗原融合,将Hoc蛋白与M2e抗原融合,将它们组装到缺乏Soc和Hoc蛋白的T4噬菌体(SocHocT4)上,从而构建一种同时呈现HA1和M2e抗原的纳米疫苗。 结果:对目标蛋白条带光密度的分析表明,每个颗粒可展示约179个HA1和68个M2e抗原分子。此外,动物实验表明,与单独用HA1和M2e抗原分子免疫相比,这种展示双抗原簇的纳米颗粒疫苗诱导了更强的特异性免疫反应、更高的抗体滴度、更平衡的Th1/Th2免疫反应以及增强的CD4和CD8 T细胞效应。重要的是,用展示双抗原簇的T4噬菌体免疫的小鼠对H3N2流感病毒实现了完全保护(100%保护),突出了其强大的保护效力。 结论:总之,我们的研究结果表明,基于展示抗原簇的T4噬菌体的颗粒具有理想的免疫原性和保护作用,为开发除流感之外的针对各种病毒的亚单位疫苗提供了一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba47/11769387/754801644060/vaccines-13-00070-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba47/11769387/6193a665305f/vaccines-13-00070-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba47/11769387/5fe102ffbf00/vaccines-13-00070-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba47/11769387/7f4ecd946d23/vaccines-13-00070-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba47/11769387/cc05a7eacb49/vaccines-13-00070-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba47/11769387/754801644060/vaccines-13-00070-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba47/11769387/6193a665305f/vaccines-13-00070-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba47/11769387/5fe102ffbf00/vaccines-13-00070-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba47/11769387/7f4ecd946d23/vaccines-13-00070-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba47/11769387/cc05a7eacb49/vaccines-13-00070-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba47/11769387/754801644060/vaccines-13-00070-g004.jpg

相似文献

[1]
T4 Phage Displaying Dual Antigen Clusters Against H3N2 Influenza Virus Infection.

Vaccines (Basel). 2025-1-13

[2]
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Vaccine. 2025-5-22

[3]
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Int J Nanomedicine. 2019-9-16

[4]
M2e-displaying virus-like particles with associated RNA promote T helper 1 type adaptive immunity against influenza A.

PLoS One. 2013-3-18

[5]
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Vaccine. 2015-6-26

[6]
[Construction and immunogenicity of recombinant bacteriophage T7 vaccine expressing M2e peptides of avian influenza virus].

Bing Du Xue Bao. 2013-6

[7]
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Virol Sin. 2019-6-25

[8]
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Vaccine. 2020-8-27

[9]
Immunization with M2e-displaying T7 bacteriophage nanoparticles protects against influenza A virus challenge.

PLoS One. 2012-9-24

[10]
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本文引用的文献

[1]
Capsid virus-like particle display improves recombinant influenza neuraminidase antigen stability and immunogenicity in mice.

iScience. 2024-5-20

[2]
Ex Pluribus Unum: The CD4 T Cell Response against Influenza A Virus.

Cells. 2024-4-5

[3]
The Promotion of Humoral Immune Responses in Humans via SOCS1-Mediated Th2-Bias Following SARS-CoV-2 Vaccination.

Vaccines (Basel). 2023-11-20

[4]
Identification of the bacteriophage nucleus protein interaction network.

Nat Struct Mol Biol. 2023-11

[5]
Self-assembled multiepitope nanovaccine based on NoV P particles induces effective and lasting protection against H3N2 influenza virus.

Nano Res. 2023

[6]
A Preliminary Study in Immune Response of BALB/c and C57BL/6 Mice with a Locally Allergic Rhinitis Model.

Am J Rhinol Allergy. 2023-7

[7]
Nanovaccines against Viral Infectious Diseases.

Pharmaceutics. 2022-11-22

[8]
A biepitope, adjuvant-free, self-assembled influenza nanovaccine provides cross-protection against H3N2 and H1N1 viruses in mice.

Nano Res. 2022

[9]
T helper type (Th1/Th2) responses to SARS-CoV-2 and influenza A (H1N1) virus: From cytokines produced to immune responses.

Transpl Immunol. 2022-2

[10]
Bacteriophage T4 Vaccine Platform for Next-Generation Influenza Vaccine Development.

Front Immunol. 2021

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