MECHANISMS OF PROTECTION IN HEPATITIS-C VIRUS-INFECTION

Little is understood about the immune response associated with hepatit is C virus (HCV) infection, let alone the mechanisms of protection tha t may be developed following infection by this virus. Clinical observa tions as well as experimental protocols performed in the chimpanzee mo del have brought evidence that protective immunity in HCV infection is weak or absent. This apparent lack of immunity was even demonstrated in cases of infected animals challenged with homologous strains of vir uses. Yet, evidence for circulating, neutralizing antibodies has been suggested by at least two studies (performed in vitro and in vivo), al though the lack of a satisfactory in vitro culture system did not allo w direct assessment of viral neutralization perse. Intrahepatic T cell s as well as proliferative responses specific for HCV antigens, namely the nucleocapsid, the envelopes E1 and E2, and the non-stuctural prot eins NS4 and NS5 have also been documented. The role of these cells in viral clearance or development of disease or both remains to be eluci dated. The emergence of apparent neutralization-resistant variants of HCV over time represents a concern for the development of HCV vaccines . Modes of immunization that favor induction of a cellular-based immun e response such as the use of DNA-immunogen might become of increasing interest for scientists willing to deal with this challenge.