Hepatocytes by DNA Vaccine–Primed

A key question in the development of a therapeutic vaccine against hepatitis C virus (HCV) is whether vaccine-primed T cells enter the liver and eliminate HCV-expressing hepa-tocytes. In the absence of an infectious small-animal model, we evaluated liver homing of vaccine-primed T cells in mice with transient hepatic transgene expression of the HCV non-structural 3/4A (NS3/4A) protein. We found that T cells primed by transdermal DNA-based vaccination entered the liver and cleared NS3/4A-expressing hepatocytes in transiently trans-genic CD8+/+ mice but not in CD8/ mice. Hence, peripherally primed NS3/4A-specific CD8+ T cells home to the liver and clear HCV protein–expressing hepatocytes. Hepatitis C virus (HCV) is highly effective at establishing a chronic infection by mechanisms that are not fully understood. Additive factors—such as immune escape by mutations [1]