GENETIC IMMUNIZATION GENERATES CELLULAR AND HUMORAL IMMUNE-RESPONSES AGAINST THE NONSTRUCTURAL PROTEINS OF THE HEPATITIS-C VIRUS IN A MURINE MODEL

Exposure to hepatitis C virus (HCV) is associated with a high prevalen ce of persistent viral infection and the development of chronic liver disease and hepatocellular carcinoma. Recovery from acute infection ma y depend upon the generation of broad-based cellular immune responses to viral structural and nonstructural proteins, We used the DNA-based immunization approach in BALB/c mice to determine whether the HCV nons tructural proteins NS3, NS4, and NS5 will induce Ab responses, CD4(+) Th cell proliferation, and cytokine release in response to stimulation by recombinant proteins as well as generate CD8(+) CTL activity both in vitro and in vivo, We found that the nonstructural proteins were pa rticularly good immunogens and produced cellular immune responses when administered as a DNA construct, Indeed, a tumor model was establishe d following inoculation of syngenic SP2/0 cells stably transfected wit h NS5, We observed protection against tumor formation and growth only in mice immunized with the NS5-encoding DNA construct, establishing th e generation of significant CTL activity in vivo by this technique. Th e results indicate that genetic immunization may define the cellular i mmune response of the host to HCV nonstructural proteins and is a prom ising approach for vaccine development.