Abstract
A single correlate of effective vaccine protection against chronic HCV infection has yet to be defined. In this study, we analyzed T-cell responses in four chimpanzees, immunized with core-E1-E2-NS3 and subsequently infected with HCV1b. Viral clearance was observed in one animal, while the other three became chronically infected. In the animal that cleared infection, NS3-specific CD8 T-cell responses were observed to be more potent in terms of frequency and polyfunctionality of cytokine producing cells. Unique to this animal was the presence of killing-competent CD8 T-cells, specific for NS31258–1272, being presented by the chimpanzee MHC class I molecule Patr-A*03∶01, and a high affinity recognition of this epitope. In the animals that became chronically infected, T-cells were able to produce cytokines against the same peptide but no cytolysis could be detected. In conclusion, in the animal that was able to clear HCV infection not only cytokine production was observed but also cytolytic potential against specific MHC class I/peptide-combinations.
Highlights
Hepatitis C virus (HCV) infection is characterized by a high propensity for development of chronic infection, which typically manifests as asymptomatic for a long period of time
The preceding study had been performed in six purpose bred, naive mature chimpanzees (Pan troglodytes) that were housed at the Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands, according to international guidelines for non-human primate care and use (The European Council Directive 86/609/EEC, and Convention ETS 123, including the revised Appendix A)
IFNc release, ex vivo lymphoproliferative responses, Th1/Th2 cytokine release patterns, and HCV-specific antibodies were comparable amongst the four animals [11]
Summary
Hepatitis C virus (HCV) infection is characterized by a high propensity for development of chronic infection, which typically manifests as asymptomatic for a long period of time. A vaccine that could prevent development of persistent HCV infection would be of great clinical benefit. The chimpanzee is the only validated animal model of HCV infection [1,2]. The dilemma that biomedical research in nonhuman primates, and chimpanzees in particular, is inevitably associated with low animal numbers and limiting statistical analysis, has been discussed elsewhere [3]. We believe that results from in depth immune-profiling of immunized chimpanzees may provide new insights into immune mechanisms operating in the early phase after infection and as such is important for optimal vaccine development in the future
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
