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双层蛋白纳米颗粒诱导针对多种流感 A 病毒的广泛保护。

Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses.

机构信息

Center for Inflammation, Immunity & Infection, Georgia State University, Atlanta, GA, 30303, USA.

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

出版信息

Nat Commun. 2018 Jan 24;9(1):359. doi: 10.1038/s41467-017-02725-4.


DOI:10.1038/s41467-017-02725-4
PMID:29367723
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5783933/
Abstract

Current influenza vaccines provide limited protection against circulating influenza A viruses. A universal influenza vaccine will eliminate the intrinsic limitations of the seasonal flu vaccines. Here we report methodology to generate double-layered protein nanoparticles as a universal influenza vaccine. Layered nanoparticles are fabricated by desolvating tetrameric M2e into protein nanoparticle cores and coating these cores by crosslinking headless HAs. Representative headless HAs of two HA phylogenetic groups are constructed and purified. Vaccinations with the resulting protein nanoparticles in mice induces robust long-lasting immunity, fully protecting the mice against challenges by divergent influenza A viruses of the same group or both groups. The results demonstrate the importance of incorporating both structure-stabilized HA stalk domains and M2e into a universal influenza vaccine to improve its protective potency and breadth. These potent disassemblable protein nanoparticles indicate a wide application in protein drug delivery and controlled release.

摘要

目前的流感疫苗对流行的甲型流感病毒提供的保护有限。通用流感疫苗将消除季节性流感疫苗的固有局限性。在这里,我们报告了一种生成双层蛋白纳米颗粒作为通用流感疫苗的方法。通过将四聚体 M2e 去溶剂化到蛋白纳米颗粒核心中,并通过交联无头 HA 来涂覆这些核心,从而制备分层纳米颗粒。构建并纯化了两个 HA 进化群的代表性无头 HA。在小鼠中用所得的蛋白纳米颗粒进行疫苗接种会引起强大的持久免疫,完全保护小鼠免受同一组或两组不同的甲型流感病毒的挑战。结果表明,将结构稳定的 HA 茎域和 M2e 结合到通用流感疫苗中对于提高其保护效力和广度非常重要。这些有效的可拆解蛋白纳米颗粒表明在蛋白药物递送和控制释放中有广泛的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/ddab25783dec/41467_2017_2725_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/78c81e202452/41467_2017_2725_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/b9158475e19f/41467_2017_2725_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/66dc128a5dac/41467_2017_2725_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/827abcc0f00b/41467_2017_2725_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/1dfb29add295/41467_2017_2725_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/3dc05bdf6ca1/41467_2017_2725_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/ddab25783dec/41467_2017_2725_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/78c81e202452/41467_2017_2725_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/b9158475e19f/41467_2017_2725_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/66dc128a5dac/41467_2017_2725_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/827abcc0f00b/41467_2017_2725_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/1dfb29add295/41467_2017_2725_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/3dc05bdf6ca1/41467_2017_2725_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bbe/5783933/ddab25783dec/41467_2017_2725_Fig7_HTML.jpg

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本文引用的文献

[1]
Alveolar macrophages are critical for broadly-reactive antibody-mediated protection against influenza A virus in mice.

Nat Commun. 2017-10-10

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Nat Commun. 2016-9-13

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Colloids Surf B Biointerfaces. 2016-8-23

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