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

Lei Tan,Kaiyan Wang,Bo Hu,Cunxia Liu,Ningyi Jin,Dan Zhang,Yanyu Liu,Huijun Lu,Mingyao Tian

doi:10.1007/s11427-011-4150-5

Abstract

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-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 LD(50) 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.

Highlights

Prophylactic DNA vaccines against the influenza virus are promising alternatives to conventional vaccines
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
To compare the abilities of the two DNA vaccines to induce hemagglutinin antigen (HA)-specific immune responses, serum samples were obtained from all the mice five weeks after the first immunization and screened for H1N1 IgG specific antibodies and hemagglutination inhibition (HI) antibodies against A/New Caledonia/20/99 (H1N1) and A/California/07/2009 (H1N1) HA antigens

Summary

Introduction

Prophylactic DNA vaccines against the influenza virus are promising alternatives to conventional vaccines. 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. 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). DNA vaccines that express the hemagglutinin (HA) protein can protect mice from the viral challenge of either influenza A or B [9−13]. Recent animal studies suggest that DNA vaccines can be delivered by in vivo electroporation (EP), resulting in high transfection efficiency and increased protein expression [14,15]. We assess the protection afforded by DNA vaccines expressing different H1N1 HAs delivered by electroporation against a lethal challenge with seasonal A/New Caledonia/20/99 (H1N1) influenza virus in a mouse model

Methods

Results

Conclusion