fax: (44) 1223 337671.
Vaccine-induced early control of hepatitis C virus infection in chimpanzees fails to impact on hepatic PD-1 and chronicity†
Article first published online: 26 FEB 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Volume 45, Issue 3, pages 602–613, March 2007
How to Cite
Rollier, C. S., Paranhos-Baccala, G., Verschoor, E. J., Verstrepen, B. E., Drexhage, J. A. R., Fagrouch, Z., Berland, J.-L., Komurian-Pradel, F., Duverger, B., Himoudi, N., Staib, C., Meyr, M., Whelan, M., Whelan, J. A., Adams, V. A., Larrea, E., Riezu, J. I., Lasarte, J. J., Bartosch, B., Cosset, F.-L., Spaan, W. J. M., Diepolder, H. M., Pape, G. R., Sutter, G., Inchauspe, G. and Heeney, J. L. (2007), Vaccine-induced early control of hepatitis C virus infection in chimpanzees fails to impact on hepatic PD-1 and chronicity. Hepatology, 45: 602–613. doi: 10.1002/hep.21573
Potential conflict of interest: Nothing to report.
- Issue published online: 26 FEB 2007
- Article first published online: 26 FEB 2007
- Manuscript Accepted: 4 JAN 2007
- Manuscript Received: 29 MAY 2006
- EC. Grant Number: QLK2-CT-1999-00356
- Instituto de Salud Carlos III. Grant Numbers: PI060149, PI051098, 03/0566
- Ministerio de Educacion y Ciencia. Grant Number: SAF2004-01680
Broad T cell and B cell responses to multiple HCV antigens are observed early in individuals who control or clear HCV infection. The prevailing hypothesis has been that similar immune responses induced by prophylactic immunization would reduce acute virus replication and protect exposed individuals from chronic infection. Here, we demonstrate that immunization of naïve chimpanzees with a multicomponent HCV vaccine induced robust HCV-specific immune responses, and that all vaccinees exposed to heterologous chimpanzee-adapted HCV 1b J4 significantly reduced viral RNA in serum by 84%, and in liver by 99% as compared to controls (P = 0.024 and 0.028, respectively). However, despite control of HCV in plasma and liver in the acute period, in the chronic phase, 3 of 4 vaccinated animals developed persistent infection. Analysis of expression levels of proinflammatory cytokines in serial hepatic biopsies failed to reveal an association with vaccine outcome. However, expression of IDO, CTLA-4 (1) and PD-1 levels in liver correlated with clearance or chronicity. Conclusion: Despite early control of virus load, a virus-associated tolerogenic-like state can develop in certain individuals independent of vaccination history. (HEPATOLOGY 2007;45:602–613.)