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含有替换的 H3 血凝素跨膜域的重组流感 H1、H5 和 H9 血凝素在小鼠中显示出增强的异源保护作用。

Recombinant influenza H1, H5 and H9 hemagglutinins containing replaced H3 hemagglutinin transmembrane domain showed enhanced heterosubtypic protection in mice.

机构信息

State Key Laboratory of Biocontrol, Life Sciences School, Sun Yat-sen University, Guangzhou, 510006, China.

Firstline Biopharmaceuticals Corporation, 12050 167th PL NE, Redmond, WA 98052, USA.

出版信息

Vaccine. 2014 May 23;32(25):3041-9. doi: 10.1016/j.vaccine.2014.03.058. Epub 2014 Apr 3.

DOI:10.1016/j.vaccine.2014.03.058
PMID:24704333
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7115591/
Abstract

Influenza A viruses cause annual epidemics and irregular pandemics. A vaccine with heterosubtypic protection (hetero-protection) has been needed. In the present study, various influenza H1, H3, H5, and H9 hemagglutinin (HA) proteins were expressed in insect cells, and then mice were subcutaneously immunized with the expressed HA proteins, and challenged by influenza A viruses (A/Puerto Rico/8/1934 (H1N1) or A/chicken/Guangdong/96 (H9N2)). The results first showed that wild-type H3 hemagglutinin (HA) (H3-WT), but not a transmembrane domain (TM) mutant, had hetero-protection against both H1N1 and H9N2 with survival rates of 17% and 33% respectively, and that wild-type H1 (H1-WT), H5 (H5-WT) and H9 (H9-WT) had no hetero-protection against H1N1 or H9N2 except for H5-WT against H1N1 with a survival rate of 17%. Then the H3-WT TM replaced the TMs of H1-WT, H5-WT and H9-WT to generate recombinant H1-TM, H5-TM and H9-TM respectively, and whether the H3-WT TM-dependent hetero-protection could be transferred to these TM mutants was investigated. The results showed that the H3-WT TM-dependent hetero-protection was transferable. H1-TM against H9N2 and H9-TM against H1N1 were with survival rates of 33% and 17% respectively, and H5-TM against both H1N1 and H9N2 with survival rates of 50% and 17% respectively. Furthermore, higher dosage H5-TM scored 100% hetero-protection against H1N1. These results demonstrated that replacement of the TMs of non-H3 HAs with H3-WT TM could enhance their hetero-protection. These findings would help the development of future influenza vaccines against pandemics such as the recently appeared H7N9 infection.

摘要

甲型流感病毒每年引起流行疫情，且不时引发大流行。因此需要一种具有异源保护作用（异源保护）的疫苗。本研究在昆虫细胞中表达了各种甲型流感 H1、H3、H5 和 H9 血凝素（HA）蛋白，然后用表达的 HA 蛋白对小鼠进行皮下免疫接种，并通过甲型流感病毒（A/Puerto Rico/8/1934（H1N1）或 A/chicken/Guangdong/96（H9N2））进行攻毒。结果首次表明，野生型 H3 血凝素（HA）（H3-WT）而非跨膜结构域（TM）突变体对 H1N1 和 H9N2 具有异源保护作用，生存率分别为 17%和 33%，野生型 H1（H1-WT）、H5（H5-WT）和 H9（H9-WT）对 H1N1 或 H9N2 除 H5-WT 对 H1N1 的生存率为 17%外，均无异源保护作用。然后用 H3-WT TM 替换 H1-WT、H5-WT 和 H9-WT 的 TM，分别生成重组 H1-TM、H5-TM 和 H9-TM，研究 H3-WT TM 依赖性异源保护作用是否可以转移到这些 TM 突变体上。结果表明，H3-WT TM 依赖性异源保护作用是可转移的。H1-TM 对 H9N2 和 H9-TM 对 H1N1 的生存率分别为 33%和 17%，H5-TM 对 H1N1 和 H9N2 的生存率分别为 50%和 17%。此外，高剂量 H5-TM 对 H1N1 的异源保护率达到 100%。这些结果表明，用 H3-WT TM 替换非 H3 HA 的 TM 可增强其异源保护作用。这些发现将有助于开发针对大流行流感的未来疫苗，如最近出现的 H7N9 感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/61976ba47066/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/d922e57912a1/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/7b7ffd37b395/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/a11c8fb3ba48/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/99fbfbd1ed51/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/98c46f83feb3/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/d1a0195f5f8d/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/61976ba47066/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/d922e57912a1/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/7b7ffd37b395/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/a11c8fb3ba48/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/99fbfbd1ed51/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/98c46f83feb3/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/d1a0195f5f8d/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a671/7115591/61976ba47066/gr7_lrg.jpg

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