Humoral response against hepatitis C virus
Abstract number: 10.1111/j.1198-743X.2004.902_s116.x
Antibodies are often a reliable marker indicating vigorous response against infectious agents and in several viral diseases presence of anti-viral antibodies indicates an effective protection. However, in the case of hepatitis C virus (HCV) in spite of an intense antibody response there is no protection against a new infection and often the virus overcomes host defences establishing a persistent infection. There is a lively debate about whether the humoral response affords any protection against HCV in the infected host. Indeed, whereas some studies have shown that a high titre of anti-HCV antibodies does not prevent reinfection, several other reports indicate the presence of a protective response consistently with the demonstration that immunoglobulins may prevent the infection in patients at risk. Finally, description of the dynamics of intra-host evolution have shown that a crucial phase for disease outcome lies at a time point corresponding to the production of antibodies by the infected host. These data suggest an important role for antibodies in the evolution of HCV infection.
An important structure studied as a target of antibody is HCV E2 envelope glycoprotein (HCV/E2), but unfortunately the assessment of the efficacy of this class of antibodies has been hampered by the poor growth efficiency of HCV in cell culture, by the fact that the murine response is not consistent with the human antibody response and by the unavailability of animal models of this infection beside primates.
Cloning of the immune repertoire of an HCV-infected patient on phage display combinatorial vectors and generation of human monoclonal antibodies have demonstrated that activity varies widely for single clones. In particular efficiency in neutralizing HCV/E2 binding to cellular target and in inhibiting infection of cells by HCV pseudoviruses is different for each clone. The observation that only some clones are able to inhibit HCV, can help understand how this virus escapes the control of the immune system. A better characterization of the anti-HCV immune response in terms of biological activity will help the design of possible vaccine strategies and their in vitro evaluation. This would be a considerable advance in an infection lacking an animal model. Molecules demonstrated in vitro to stimulate selectively the production of neutralizing antibody clones will be the best candidates for further in vivo studies."
|Session name:||XXIst ISTH Congress|
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