Hepatitis Research Today is a free monthly online journal that collates and summarizes the latest research about Hepatitis, including details on hepatitis a, b, c, causes, symptoms. | ||||||||
|
CD4+ immune escape and subsequent T-cell failure following chimpanzee immunization against hepatitis C virus.Puig M, Mihalik K, Tilton JC, Williams O, Merchlinsky M, Connors M, Feinstone SM, Major ME Laboratory of Hepatitis Viruses, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. Hepatitis C is a major cause of chronic liver disease, with 170 million individuals infected worldwide and no available vaccine. We analyzed the effects of an induced T-cell response in 3 chimpanzees, targeting nonstructural proteins in the absence of neutralizing antibodies. In all animals the specific T-cell response modified the outcome of infection, producing a 10- to 1,000-fold reduction in peak virus titers. The challenge of 2 immunized animals that had been previously exposed to hepatitis C virus resulted in subclinical infections. Immune responses in the third animal, naive prior to immunization, limited viral replication immediately, evidenced by a 30-fold reduction in virus titer by week 2, declining to a nonquantifiable level by week 6. After 10 weeks of immunological control, we observed a resurgence of virus, followed by progression to a persistent infection. Comparing virus evolution with T-cell recognition, we demonstrated that: (i) resurgence was concomitant with the emergence of new dominant viral populations bearing single amino acid changes in the NS3 and NS5A regions, (ii) these mutations resulted in a loss of CD4+ T-cell recognition, and (iii) subsequent to viral resurgence and immune escape a large fraction of NS3-specific T cells became impaired in their ability to secrete IFN-gamma and proliferate. In contrast, NS3-specific responses were sustained in the recovered/immunized animals presenting with subclinical infections. In conclusion, viral escape from CD4+ T cells can result in the eventual failure of an induced T-cell response that initially controls infection. Vaccines that can induce strong T-cell responses prior to challenge will not necessarily prevent persistent HCV infection. Published 4 September 2006 in Hepatology, 44(3): 736-45.
© 2006-2008 Hepatitis Research Today. All Rights Reserved. |
| ||||||
