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

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.