Efficacy of seasonal pandemic influenza hemagglutinin DNA vaccines delivered by electroporation against aseasonal H1N1 virus challenge in mice  

作　　者：TAN Lei LU HuiJun ZHANG Dan WANG KaiYan TIAN MingYao LIU CunXia LIU YanYu HU Bo JIN NingYi 

机构地区：[1]Genetic Engineering Laboratory of PLA, Academy of Military Medical Sciences of PLA, Changchun 130062, China [2]College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China [3]Agricultural College of Yanbian University, Yanji 133400, China

出　　处：《Science China(Life Sciences)》2011年第4期293-299,共7页中国科学（生命科学英文版）

基　　金：supported by the National High Technology Research and Development Program of China(Grant No.2006AA10A205);the National Key Technology Research and Development Program(Grant No. 2006BAD06A05);the National Key Program for Infectious Diseases of China(Grant No.2009ZX10004-103)

摘　　要：Prophylactic DNA vaccines against the influenza virus are promising alternatives to conventional vaccines. In this study, we generated two candidate gene-based influenza vaccines encoding either the seasonal or pandemic hemagglutinin antigen （HA） from the strains A/New Caledonia/20/99 （HIN1） （pV1AS） and A/Califorrtia/04/2009 （H1N1） （pVEH1）, respectively. After verifying antigen expression, the immunogenicity of the vaccines delivered intramuscularly with electroporation was tested in a mouse model. Sera of immunized animals were tested in hemagglutination inhibition assays and by ELISA for the presence of HA-specific antibodies. HA-specific T-cells were also measured in IFN-γ ELISpot assays. The protective efficacy of the candidate influenza vaccines was evaluated by measuring mortality rates and body weight after a challenge with 100 LD50 of mouse-adapted A/New Caledonia/20/99 （H1N1）. Mice immunized with either one of the two vaccines showed significantly higher T cell and humoral immune responses （P〈0.05） than the pVAX1 control group. Additionally, the pV1A5 vaccine effec- tively protected the mice against a lethal homologous mouse-adapted virus challenge with a survival rate of 100% compared with a 40% survival rate in the pVEH1 vaccinated group （P〈0.05）. Our study indicates that the seasonal influenza DNA vac- cine completely protects against the homologous A/New Caledonia/20/99 virus （H1N1）, while the pandemic influenza DNA vaccine only partially protects against this virus.Prophylactic DNA vaccines against the influenza virus are promising alternatives to conventional vaccines.In this study,we generated two candidate gene-based influenza vaccines encoding either the seasonal or pandemic hemagglutinin antigen(HA) from the strains A/New Caledonia/20/99(H1N1)(pV1A5) and A/California/04/2009(H1N1)(pVEH1) ,respectively.After verifying antigen expression,the immunogenicity of the vaccines delivered intramuscularly with electroporation was tested in a mouse model.Sera of immunized animals were tested in hemagglutination inhibition assays and by ELISA for the presence of HA-specific antibodies.HA-specific T-cells were also measured in IFN-γELISpot assays.The protective efficacy of the candidate influenza vaccines was evaluated by measuring mortality rates and body weight after a challenge with 100 LD50 of mouse-adapted A/New Caledonia/20/99(H1N1) .Mice immunized with either one of the two vaccines showed significantly higher T cell and humoral immune responses(P<0.05) than the pVAX1 control group.Additionally,the pV1A5 vaccine effectively protected the mice against a lethal homologous mouse-adapted virus challenge with a survival rate of 100%compared with a 40%survival rate in the pVEH1 vaccinated group(P<0.05) .Our study indicates that the seasonal influenza DNA vaccine completely protects against the homologous A/New Caledonia/20/99 virus(H1N1) ,while the pandemic influenza DNA vaccine only partially protects against this virus.

关 键 词：seasonal influenza pandemic influenza HEMAGGLUTININ DNA vaccine ELECTROPORATION H1N1 influenza virus 

分 类 号：S942.5[农业科学—水产养殖] S855.3[农业科学—水产科学]