(Mehta et al., 2002). Some hepatitis C vaccine candidates have shown similar potential (Forns et al., 2000; Weiner et al., 2001).

Although those clinical observations suggest that it is possible to develop a vaccine to prevent chronic HCV infection, there are important challenges. Immunity produced by natural infection does not prevent reinfection (that is, it is not sterilizing); such immunity reduces the frequency of chronic infection but does not prevent it (Farci et al., 1992). Moreover, the immunologic correlates of those critical clinical outcomes are not sufficiently understood for rational design or evaluation of vaccine products. Marked genetic variability in some HCV epitopes creates an especially formidable challenge if immunity to them is necessary for protection.

Although HCV infections occur in the general population of the United States and other economically developed countries, the incidence is probably too low to justify universal HCV vaccination. A hepatitis C vaccine is most likely to benefit populations that are at highest risk, include IDUs, health-care workers who perform high-risk procedures, and some men who report high-risk sexual practices with other men. A vaccine that prevents chronic HCV infection not only might reduce the likelihood of long-term disease, such as cirrhosis or HCC, but might reduce the likelihood of secondary transmission by reducing the infection reservoir. It may not be possible to produce a vaccine that prevents HCV infection, but a product that prevents acute HCV infections from becoming chronic would probably achieve many of the same benefits. In cases where acute HCV infection does not resolve within a few months, early treatment can prevent most cases from evolving into chronic HCV infection. However, because most acute HCV infections are not recognized, a vaccine is further likely to be of greatest benefit to populations in whom acute infection is rarely recognized and treated (for example, IDUs).

Estimates of the cost effectiveness of hepatitis C vaccination depend on a number of factors, including the cost of the vaccine, the target population’s incidence, and projections of its effectiveness and duration. Several studies have evaluated the potential cost effectiveness of an HCV vaccine that prevents acute (and chronic) infection. Krahn et al. (2005) calculated that if a hepatitis C vaccine with 80% efficacy was available, had a duration of effectiveness equivalent to that of the hepatitis B vaccine, and was cost-equivalent to that of the current hepatitis A vaccine ($51 per dose plus administration fees), it would be cost saving to vaccinate IDUs. The authors