Recombinant influenza H1, H5 and H9 hemagglutinins containing replaced H3 hemagglutinin transmembrane domain showed enhanced heterosubtypic protection in mice.
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.
State Key Laboratory of Biocontrol, Life Sciences School, Sun Yat-sen University, Guangzhou, 510006, China.
Qiliang
Q
Liu
State Key Laboratory of Biocontrol, Life Sciences School, Sun Yat-sen University, Guangzhou, 510006, China.
Kang
K
Liu
State Key Laboratory of Biocontrol, Life Sciences School, Sun Yat-sen University, Guangzhou, 510006, China.
Chunyi
C
Xue
State Key Laboratory of Biocontrol, Life Sciences School, Sun Yat-sen University, Guangzhou, 510006, China.
Jianqiang
J
Zhou
State Key Laboratory of Biocontrol, Life Sciences School, Sun Yat-sen University, Guangzhou, 510006, China.
Xiaoming
X
Li
State Key Laboratory of Biocontrol, Life Sciences School, Sun Yat-sen University, Guangzhou, 510006, China.
Dongyu
D
Luo
State Key Laboratory of Biocontrol, Life Sciences School, Sun Yat-sen University, Guangzhou, 510006, China.
Jing
J
Zheng
State Key Laboratory of Biocontrol, Life Sciences School, Sun Yat-sen University, Guangzhou, 510006, China.
Shun
S
Xu
Firstline Biopharmaceuticals Corporation, 12050 167th PL NE, Redmond, WA 98052, USA.
George Dacai
GD
Liu
State Key Laboratory of Biocontrol, Life Sciences School, Sun Yat-sen University, Guangzhou, 510006, China. Electronic address: caoych@mail.sysu.edu.cn.
Yongchang
Y
Cao
D000595:Amino Acid Sequence; D000818:Animals; D056738:Cross Protection; D016207:Cytokines / Q000276:immunology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000145:classification / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype; D053127:Influenza A Virus, H9N2 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000276:immunology; D061987:Sf9 Cells
D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins
Hemagglutinin; Immune response; Influenza A virus; Subunit vaccine