Immunogenicity of candidate hepatitis E virus DNA vaccine expressing complete and truncated ORF2 in mice

Abstract

Hepatitis E virus (HEV) is a major cause of enterically transmitted acute hepatitis of adults in developing nations. Our present studies show that, the complete ORF2 gene (1-660 amino acids, a.a.) coding for capsid protein of HEV as candidate DNA vaccine induced significant specific humoral and cellular immune responses in mice. Gene gun based DNA administration led to higher seroconversion rates and HEV-specific antibody titers as against needle-injection method. The region (458-607 a.a.) within ORF2 protein is reported to harbour the predominant neutralization epitope/s (NE) of HEV. The NE DNA also induced HEV-specific immune responses in mice. NE-based DNA-prime-protein boost approach was observed to be superior to NE DNA based approach. Co-administration of plasmid expressing mouse granulocyte macrophage colony stimulating factor (GM-CSF) induced immune response at similar level as that with ORF2/NE plasmid alone. IgG1 was the predominant isotype irrespective of the approach used. HEV-specific antibodies in seroconverted mice sera could bind/neutralize HEV in an in vitro ELISA-based assay. In conclusion, efficacy of ORF2 and NE based DNA/DNA-prime-protein-boost approaches are worth exploring in monkey model.