IMMUNITY ELICITED BY HEPATITIS-C VIRUS

Hepatitis C virus (HCV), the major causative agent of post-transfusion and community-acquired non-A, non-B (NANB), is a single-stranded RNA virus characterized by a high degree of genetic heterogeneity. HCV is endemic worldwide and is a major cause of chronic liver disease and he patocellular carcinoma. The development of a broadly reactive vaccine is a high priority for the control of HCV infection. In recent years, however, serious concerns have been raised regarding the degree of pro tective immunity elicited by HCV in the host. Several observations, bo th inpatients and in the chimpanzee model, have suggested a lack of pr otective immunity against HCV. Chronic HCV infection develops in more than 80% of patients, suggesting that in most cases the immune respons e of the host fails to mediate resolution of the infection. Cross-chal lenge studies demonstrated that convalescent chimpanzees are not prote cted against re-infection with homologous or heterologous HCV strains. Similar evidence has been obtained in polytransfused beta-thalassemic children, in whom re-infection with HCV was associated with multiple episodes of acute hepatitis. Although most of the evidence thus far ac cumulated suggests that HCV does not elicit a protective immune respon se, recent studies have provided experimental evidence, both in vitro and in vivo, that HCV infection induces a neutralizing antibody respon se in humans. However, such antibodies are isolate-restricted and inef fective against variant HCV strains emerging in vivo. Recently, using recombinant envelope proteins of HCV, a successful vaccination of chim panzees against challenge with a homologous viral strain was reported Whether this vaccine can provide protection against challenge with a h igher infectious dose of the homologous virus or against challenge wit h heterologous strains of HCV remains to be established. Overall, the data hitherto accumulated indicate that the genetic heterogeneity of H CV will be a major impediment for the development of a broadly reactiv e vaccine for the control of HCV infection.