Recombinant influenza H1, H5 and H9 hemagglutinins containing replaced H3 hemagglutinin transmembrane domain showed enhanced heterosubtypic protection in mice.
Recombinant influenza H1, H5 and H9 hemagglutinins containing replaced H3 hemagglutinin transmembrane domain showed enhanced heterosubtypic protection in mice.
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DOI：
10.1016/j.vaccine.2014.03.058
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发表时间：
2014-05-23
期刊：
影响因子：
5.5
通讯作者：
Cao Y
中科院分区：
文献类型：
--
作者：
Liu Q;Liu K;Xue C;Zhou J;Li X;Luo D;Zheng J;Xu S;Liu GD;Cao Y
我们发现H3-WT跨膜结构域对于H3 HA诱导的异源保护是至关重要的。野生型H3显示出比H1、H5和H9 HA更多的异源保护。替换的跨膜结构域对Sf 9细胞中H1、H5和H9 HA蛋白的体外表达没有明显影响。具有H3跨膜结构域蛋白的HA表现出增强的异亚型保护。甲型流感病毒引起每年的流行病和不定期的大流行。需要具有异亚型保护（hetero-protection）的疫苗。在本研究中，多种流感H1、H3、H5和H9血凝素（HA）蛋白在昆虫细胞中表达，然后用表达的HA蛋白皮下免疫小鼠，并用A型流感病毒（A/波多黎各/8/1934（H1N1）或A/鸡/广东/96（H9 N2））攻击。结果首先表明，野生型H3血凝素（HA）（H3-WT），而不是跨膜结构域（TM）突变体，对H1N1和H9 N2都具有异源保护作用，存活率分别为17%和33%，而野生型H1（H1-WT），H5（H5-WT）和H9（H9-WT）没有针对H1N1或H9 N2的异源保护，除了针对H1N1的H5-WT存活率为17%。然后将H3-WT TM分别替换H1-WT、H5-WT和H9-WT的TM，分别得到重组的H1-TM、H5-TM和H9-TM，并研究了H3-WT TM依赖的异源保护是否能转移到这些TM突变体中。结果表明，H3-WT TM依赖的异源保护是可转移的。抗H9 N2的H1-TM和抗H1N1的H9-TM的存活率分别为33%和17%，抗H1N1和H9 N2的H5-TM的存活率分别为50%和17%。此外，更高剂量的H5-TM对H1N1的异质保护达到100%。这些结果表明，用H3-WT TM替换非H3 HA的TM可以增强其杂保护。这些发现将有助于开发未来的流感疫苗，以对抗最近出现的H7N9感染等大流行病。
We found H3-WT transmembrane domain is critical for H3 HA-induced hetero-protection. Wild-type H3 showed more hetero-protection than H1, H5 and H9 HAs. Replaced transmembrane domain had no apparent impact on in vitro expression of H1, H5 and H9 HA proteins in Sf9 cells. HAs with H3 transmembrane domain proteins exhibited enhanced heterosubtypic protections. 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.
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影响因子：
6.7
作者：
Tong S;Zhu X;Li Y;Shi M;Zhang J;Bourgeois M;Yang H;Chen X;Recuenco S;Gomez J;Chen LM;Johnson A;Tao Y;Dreyfus C;Yu W;McBride R;Carney PJ;Gilbert AT;Chang J;Guo Z;Davis CT;Paulson JC;Stevens J;Rupprecht CE;Holmes EC;Wilson IA;Donis RO
通讯作者：
Donis RO
影响因子：
82.9
作者：
Neirynck, S;Deroo, T;Fiers, W
通讯作者：
Fiers, W
影响因子：
5.4
作者：
Quan, Fu-Shi;Huang, Chunzi;Kang, Sang-Moo
通讯作者：
Kang, Sang-Moo
影响因子：
5.4
作者：
LITTELVANDENHURK, SV;PARKER, MD;BABIUK, LA
通讯作者：
BABIUK, LA
影响因子：
2.9
作者：
Park, PSH;Wells, JW
通讯作者：
Wells, JW