Why is it so difficult to develop a hepatitis C virus preventive vaccine?

With an estimated 3% of the world's population chronically infected, hepatitis C virus (HCV) represents a major health problem for which an efficient vaccination strategy would be highly desirable. Indeed, chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocarcinoma and liver failure worldwide and it is the most common indication for liver transplantation, accounting for 40-50% of liver transplants. Much progress has been made in the prevention of HCV transmission and in therapeutic intervention. However, even if a new wave of directly acting antivirals promise to overcome the problems of low efficacy and adverse effects observed for the current standard of care, which include interferon-α and ribavirin, an effective vaccine would be the only means to definitively eradicate infection and to diminish the burden of HCV-related diseases at affordable costs. Although there is strong evidence that the goal of a prophylactic vaccine could be achieved, there are huge development issues that have impeded reaching this goal and that still have to be addressed. In this article we address the question of whether an HCV vaccine is needed, whether it will eventually be feasible, and why it is so difficult to produce.