Intrahepatic genetic inoculation of hepatitis C virus RNA confers cross-protective immunity

Naturally occurring hepatitis C virus (HCV) infection has long been thought to induce a weak immunity which is insufficient to protect an individual f rom subsequent infections and has cast doubt on the ability to develop effe ctive vaccines. A series of intrahepatic genetic inoculations (IHGI) with t ype la HCV RNA were performed in a chimpanzee to determine whether a form o f genetic immunization might stimulate protective immunity. We demonstrate that the chimpanzee not only developed protective immunity to the homologou s type la RNA after rechallenge by IHGI but was also protected from chronic HCV infection after sequential rechallenge with 100 50% chimpanzee infecti ous doses of a heterologous type la (H77) and Ib (HC-J4) whole-virus inocul um. These results offer encouragement to pursue the development of HCV vacc ines.