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甲型流感病毒HA2和M2e片段与鞭毛蛋白的连接顺序对重组蛋白性质的影响

Influence of the Linking Order of Fragments of HA2 and M2e of the influenza A Virus to Flagellin on the Properties of Recombinant Proteins.

作者信息

Stepanova L A, Kotlyarov R Y, Shuklina M A, Blochina E A, Sergeeva M V, Potapchuk M V, Kovaleva A A, Ravin N V, Tsybalova L M

机构信息

Research Institute of Influenza, Russian Federation Ministry of Health, Prof. Popova Str.15/17, St. Petersburg, 197376, Russia.

Institute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Ave. 33, bldg. 2, Moscow, 119071, Russia.

出版信息

Acta Naturae. 2018 Jan-Mar;10(1):85-94.

DOI:
PMID:29713522
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5916737/
Abstract

The ectodomain of the M2 protein (M2e) and the conserved fragment of the second subunit of hemagglutinin (HA2) are promising candidates for broadly protective vaccines. In this paper, we report on the design of chimeric constructs with differing orders of linkage of four tandem copies of M2e and the conserved fragment of HA2 (76-130) from phylogenetic group II influenza A viruses to the C-terminus of flagellin. The 3D-structure of two chimeric proteins showed that interior location of the M2e tandem copies (Flg-4M2e-HA2) provides partial α-helix formation nontypical of native M2e on the virion surface. The C-terminal position of the M2e tandem copies (Flg-HA2-4M2e) largely retained its native M2e conformation. These conformational differences in the structure of the two chimeric proteins were shown to affect their immunogenic properties. Different antibody levels induced by the chimeric proteins were detected. The protein Flg-HA2-4M2e was more immunogenic as compared to Flg-4M2e-HA2, with the former offering full protection to mice against a lethal challenge. We obtained evidence suggesting that the order of linkage of target antigens in a fusion protein may influence the 3D conformation of the chimeric construct, which leads to changes in immunogenicity and protective potency.

摘要

M2蛋白的胞外域（M2e）和血凝素第二亚基的保守片段（HA2）是具有广泛保护作用疫苗的有前景的候选物。在本文中，我们报道了将来自第二系统发生组甲型流感病毒的四个串联拷贝的M2e和HA2的保守片段（76 - 130）以不同连接顺序连接到鞭毛蛋白C末端的嵌合构建体的设计。两种嵌合蛋白的三维结构表明，M2e串联拷贝的内部位置（Flg - 4M2e - HA2）在病毒体表面提供了天然M2e非典型的部分α - 螺旋形成。M2e串联拷贝的C末端位置（Flg - HA2 - 4M2e）在很大程度上保留了其天然M2e构象。结果表明，这两种嵌合蛋白结构上的这些构象差异会影响它们的免疫原性。检测到嵌合蛋白诱导的不同抗体水平。与Flg - 4M2e - HA2相比，蛋白Flg - HA2 - 4M2e具有更强的免疫原性，前者能为小鼠提供针对致死性攻击的完全保护。我们获得的证据表明，融合蛋白中靶抗原的连接顺序可能会影响嵌合构建体的三维构象，进而导致免疫原性和保护效力的变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/bc0a8210e101/AN20758251-10-01-085-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/7ac830262f63/AN20758251-10-01-085-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/f37d5939662e/AN20758251-10-01-085-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/bb0c6e4479bf/AN20758251-10-01-085-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/f483e5792c4c/AN20758251-10-01-085-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/7e3b1ae53da2/AN20758251-10-01-085-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/ab5134999bb7/AN20758251-10-01-085-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/cbfc181a71b1/AN20758251-10-01-085-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/bc0a8210e101/AN20758251-10-01-085-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/7ac830262f63/AN20758251-10-01-085-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/f37d5939662e/AN20758251-10-01-085-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/bb0c6e4479bf/AN20758251-10-01-085-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/f483e5792c4c/AN20758251-10-01-085-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/7e3b1ae53da2/AN20758251-10-01-085-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/ab5134999bb7/AN20758251-10-01-085-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/cbfc181a71b1/AN20758251-10-01-085-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8148/5916737/bc0a8210e101/AN20758251-10-01-085-g008.jpg

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Influence of the Linking Order of Fragments of HA2 and M2e of the influenza A Virus to Flagellin on the Properties of Recombinant Proteins.

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引用本文的文献

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[2]
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本文引用的文献

[1]
A Fusion Protein Based on the Second Subunit of Hemagglutinin of Influenza A/H2N2 Viruses Provides Cross Immunity.

Acta Naturae. 2016

[2]
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

[3]
Protection against multiple influenza A virus strains induced by candidate recombinant vaccine based on heterologous M2e peptides linked to flagellin.

PLoS One. 2015-3-23

[4]
Heterosubtypic protection against influenza A induced by adenylate cyclase toxoids delivering conserved HA2 subunit of hemagglutinin.

Antiviral Res. 2012-10-2

[5]
A virus-like particle that elicits cross-reactive antibodies to the conserved stem of influenza virus hemagglutinin.

J Virol. 2012-8-15

[6]
Unipro UGENE: a unified bioinformatics toolkit.

Bioinformatics. 2012-2-24

[7]
A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins.

Science. 2011-7-28

[8]
A highly conserved neutralizing epitope on group 2 influenza A viruses.

Science. 2011-7-7

[9]
Immunogenicity and efficacy of flagellin-fused vaccine candidates targeting 2009 pandemic H1N1 influenza in mice.

PLoS One. 2011-6-7

[10]
Safety and immunogenicity of a recombinant M2e-flagellin influenza vaccine (STF2.4xM2e) in healthy adults.

Vaccine. 2011-5-30

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