LAUSR

humans. The need for a new model of HCV infection is acute. DAA therapy will likely have limited impact on HCV disease burden in the foreseeable future. Most HCV infections are undiagnosed and virus transmission is increasing in many regions of the world because of an epidemic in opioid use. There is no vaccine to prevent HCV transmission. Hopes are now pinned on a single vaccine approach that elicits T-cell immunity against nonstructural HCV proteins. Proof-of-concept studies in chimpanzees suggest that this unique approach might prevent HCV persistence. Immunization of human volunteers with recombinant virus vectors expressing these nonstructural HCV proteins also generated pan-genotypic T-cell immunity. The vaccine is now being evaluated for protection in individuals at risk for infection. Despite this progress, mechanisms of protective immunity remain uncertain. Whether T cells, antibodies, or both will be required to protect against primary HCV infection, or reinfection after costly antiviral cure of CHC, is unknown. The door to chimpanzee HCV research is now firmly closed, but a timely new door has opened with the discovery of a highly related hepacivirus that infects rats and mice. It represents a critically important advance with the potential to provide insight into subversion of immunity by hepaciviruses and facilitate further development of vaccines to stop transmission of virus that continues to impose a significant public health cost.