Chronic hepatitis C virus (HCV) infection is a major health problem worldwide, affecting
approximately 3% of the human population. Although decades of research have amassed since the virus
was characterized in 1989, there remains no prophylactic HCV vaccine approved for clinical use. The
vast genetic variability of HCV, together with weak host immune responses following infection, and a
paucity of suitable animal models for HCV vaccine research, have made HCV an elusive vaccine target.
Despite the recent advances in medical treatment enjoyed by wealthy nations, there remains an unmet
need for an affordable, effective, and accessible means to control HCV disease burden in areas of limited
resources, where HCV is most problematic. To this end, several promising HCV vaccine candidates have
been reported in recent preclinical and clinical trials. Here we review HCV virology and immunology
relevant to rational design of a prophylactic HCV vaccine, and recent studies of preclinical and clinical
HCV vaccine candidates.