OPTIMAL INDUCTION OF HEPATITIS-C VIRUS ENVELOPE-SPECIFIC IMMUNITY BY BICISTRONIC PLASMID DNA INOCULATION WITH THE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GENE

In this study, we have constructed various DNA vaccine vectors that ca rried hepatitis C virus (HCV) envelope genes without and with the gran ulocyte-macrophage colony-stimulating factor (GM-CSF) gene in several different ways. In Buffalo rats that received plasmids carrying the HC V envelope genes, which encode envelope proteins El and E2, both antib ody and lymphoproliferative responses against these proteins were indu ced. These responses were greatly enhanced by the codelivery of the GM -CSF gene. In particular, inoculation with a bicistronic plasmid that independently expressed the GM-CSF gene and the envelope genes in the same construct generated the highest antibody titers and significantly increased lymphoproliferative responses against these proteins. Moreo ver, strong antibody responses to homologous and heterologous hypervar iable region 1 peptides were elicited in the immunized rats.