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Journal of Virology, January 2004, p. 187-196, Vol. 78, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.1.187-196.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Control of Heterologous Hepatitis C Virus Infection in Chimpanzees Is Associated with the Quality of Vaccine-Induced Peripheral T-Helper Immune Response

C. Rollier,1 E. Depla,2 J. A. R. Drexhage,1 E. J. Verschoor,1 B. E. Verstrepen,1 A. Fatmi,3 C. Brinster,3 A. Fournillier,3 J. A. Whelan,4 M. Whelan,4 D. Jacobs,2 G. Maertens,2 G. Inchauspé,3* and J. L. Heeney1

Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands,1 Innogenetics, B-9052 Ghent-Zwijnaarde, Belgium,2 UMR 2142 CNRS/BioMerieux, 69007 Lyon, France,3 Onyvax Ltd., St. George Hospital Medical School, SW17 ORE London, United Kingdom4

Received 16 June 2003/ Accepted 12 September 2003

Prophylactic hepatitis C virus (HCV) vaccine trials with human volunteers are pending. There is an important need for immunological end points which correlate with vaccine efficacy and which do not involve invasive procedures, such as liver biopsies. By using a multicomponent DNA priming-protein boosting vaccine strategy, naïve chimpanzees were immunized against HCV structural proteins (core, E1, and E2) as well as a nonstructural (NS3) protein. Following immunization, exposure to the heterologous HCV 1b J4 subtype resulted in a peak of plasma viremia which was lower in both immunized animals. Compared to the naïve infection control and nine additional historical controls which became chronic, vaccinee 2 (Vac2) rapidly resolved the infection, while the other (Vac1) clearly controlled HCV infection. Immunization induced antibodies, peptide-specific gamma interferon (IFN-{gamma}), protein-specific lymphoproliferative responses, IFN-{gamma}, interleukin-2 (IL-2), and IL-4 T-helper responses in both vaccinees. However, the specificities were markedly different: Vac2 developed responses which were lower in magnitude than those of Vac1 but which were biased towards Th1-type cytokine responses for E1 and NS3. This proof-of-principle study in chimpanzees revealed that immunization with a combination of nonstructural and structural antigens elicited T-cell responses associated with an alteration of the course of infection. Our findings provide data to support the concept that the quality of the response to conserved epitopes and the specific nature of the peripheral T-helper immune response are likely pivotal factors influencing the control and clearance of HCV infection.

* Corresponding author. Mailing address: UMR 2142 CNRS/Bio-Merieux, 46 allee d'Italie, 69007 Lyon, France. Phone: 33 4 72 72 85 90. Fax: 33 4 72 72 85 33. E-mail: Genevieve.Inchauspe{at}ens-lyon.fr.

Journal of Virology, January 2004, p. 187-196, Vol. 78, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.1.187-196.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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