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向皮肤递送含有流感病毒异源M2e胞外结构域的病毒样颗粒的微针贴片可诱导广泛的异亚型交叉保护。

Microneedle patch delivery to the skin of virus-like particles containing heterologous M2e extracellular domains of influenza virus induces broad heterosubtypic cross-protection.

作者信息

Kim Min-Chul, Lee Jeong Woo, Choi Hyo-Jick, Lee Yu-Na, Hwang Hye Suk, Lee Jongsang, Kim Cheol, Lee Jong Seok, Montemagno Carlo, Prausnitz Mark R, Kang Sang-Moo

机构信息

Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Animal and Plant Quarantine Agency, 175 Anyangro, Anyang, Gyeonggido 430-757, South Korea.

School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.

出版信息

J Control Release. 2015 Jul 28;210:208-16. doi: 10.1016/j.jconrel.2015.05.278. Epub 2015 May 21.

DOI:10.1016/j.jconrel.2015.05.278
PMID:26003039
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4489561/
Abstract

A broadly cross-protective influenza vaccine that can be administrated by a painless self-immunization method would be a value as a potential universal mass vaccination strategy. This study developed a minimally-invasive microneedle (MN) patch for skin vaccination with virus-like particles containing influenza virus heterologous M2 extracellular (M2e) domains (M2e5x VLPs) as a universal vaccine candidate without adjuvants. The stability of M2e5x VLP-coated microneedles was maintained for 8weeks at room temperature without losing M2e antigenicity and immunogenicity. MN skin immunization induced strong humoral and mucosal M2e antibody responses and conferred cross-protection against heterosubtypic H1N1, H3N2, and H5N1 influenza virus challenges. In addition, M2e5x VLP MN skin vaccination induced T-helper type 1 responses such as IgG2a isotype antibodies and IFN-γ producing cells at higher levels than those by conventional intramuscular injection. These potential immunological and logistic advantages for skin delivery of M2e5x VLP MN vaccines could offer a promising approach to develop an easy-to-administer universal influenza vaccine.

摘要

一种可通过无痛自我免疫方法接种的具有广泛交叉保护作用的流感疫苗，作为一种潜在的通用大规模疫苗接种策略将具有重要价值。本研究开发了一种微创微针（MN）贴片，用于皮肤接种含有流感病毒异源M2细胞外（M2e）结构域（M2e5x VLPs）的病毒样颗粒，作为无佐剂的通用疫苗候选物。M2e5x VLP包被的微针在室温下稳定性可维持8周，且不会丧失M2e抗原性和免疫原性。MN皮肤免疫诱导了强烈的体液和黏膜M2e抗体反应，并对异源亚型H1N1、H3N2和H5N1流感病毒攻击提供了交叉保护。此外，M2e5x VLP MN皮肤接种诱导的1型辅助性T细胞反应，如IgG2a同种型抗体和产生IFN-γ的细胞，其水平高于传统肌肉注射。M2e5x VLP MN疫苗皮肤给药的这些潜在免疫和后勤优势，可为开发一种易于接种的通用流感疫苗提供一种有前景的方法。

相似文献

[1]
Microneedle patch delivery to the skin of virus-like particles containing heterologous M2e extracellular domains of influenza virus induces broad heterosubtypic cross-protection.

J Control Release. 2015-7-28

[2]
Co-immunization with tandem repeat heterologous M2 extracellular proteins overcomes strain-specific protection of split vaccine against influenza A virus.

Antiviral Res. 2015-10

[3]
Influenza M2 virus-like particles confer a broader range of cross protection to the strain-specific pre-existing immunity.

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[4]
Intranasal vaccination with M2e5x virus-like particles induces humoral and cellular immune responses conferring cross-protection against heterosubtypic influenza viruses.

PLoS One. 2018-1-11

[5]
Co-Delivery of M2e Virus-Like Particles with Influenza Split Vaccine to the Skin Using Microneedles Enhances the Efficacy of Cross Protection.

Pharmaceutics. 2019-4-18

[6]
Supplementation of influenza split vaccines with conserved M2 ectodomains overcomes strain specificity and provides long-term cross protection.

Mol Ther. 2014-7

[7]
Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity.

J Control Release. 2014-1-11

[8]
Development of a candidate influenza vaccine based on virus-like particles displaying influenza M2e peptide into the immunodominant region of hepatitis B core antigen: Broad protective efficacy of particles carrying four copies of M2e.

Vaccine. 2015-6-26

[9]
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[10]
Supplementation of H1N1pdm09 split vaccine with heterologous tandem repeat M2e5x virus-like particles confers improved cross-protection in ferrets.

Vaccine. 2016-1-20

引用本文的文献

[1]
A Bibliometric Analysis of Microneedle-Mediated Drug Delivery: Trends, Hotspots, and Future Directions.

Drug Des Devel Ther. 2025-5-10

[2]
Delivery of PLGA-Loaded Influenza Vaccine Microparticles Using Dissolving Microneedles Induces a Robust Immune Response.

Pharmaceutics. 2025-4-12

[3]
Vaccine-Induced Immunity Elicited by Microneedle Delivery of Influenza Ectodomain Matrix Protein 2 Virus-like Particle (M2e VLP)-Loaded PLGA Nanoparticles.

Int J Mol Sci. 2023-6-25

[4]
Enhanced Immunogenicity of an Influenza Ectodomain Matrix-2 Protein Virus-like Particle (M2e VLP) Using Polymeric Microparticles for Vaccine Delivery.

Viruses. 2022-8-30

[5]
Progress towards the Development of a Universal Influenza Vaccine.

Viruses. 2022-7-30

[6]
Recent Progress in Recombinant Influenza Vaccine Development Toward Heterosubtypic Immune Response.

Front Immunol. 2022

[7]
Transdermal Vaccination with the Matrix-2 Protein Virus-like Particle (M2e VLP) Induces Immunity in Mice against Influenza A Virus.

Vaccines (Basel). 2021-11-15

[8]
Microarray patches enable the development of skin-targeted vaccines against COVID-19.

Adv Drug Deliv Rev. 2021-4

[9]
Influenza-Host Interplay and Strategies for Universal Vaccine Development.

Vaccines (Basel). 2020-9-20

[10]
Progress in microneedle array patch (MAP) for vaccine delivery.

Hum Vaccin Immunother. 2021-1-2

本文引用的文献

[1]
Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity.

J Control Release. 2014-1-11

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Trends Microbiol. 2013-5-17

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Influenza virus-like particles containing M2 induce broadly cross protective immunity.

PLoS One. 2011-1-18

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Skin vaccination against cervical cancer associated human papillomavirus with a novel micro-projection array in a mouse model.

PLoS One. 2010-10-18

[10]
Dose sparing enabled by skin immunization with influenza virus-like particle vaccine using microneedles.

J Control Release. 2010-8-6

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