Strong vaccine-induced CD8 T-cell responses have cytolytic function in a chimpanzee clearing HCV infection

Babs E Verstrepen; Ernst J Verschoor; Zahra C Fagrouch; Petra Mooij; Natasja G de Groot; Ronald E Bontrop; Willy M Bogers; Jonathan L Heeney; Gerrit Koopman

doi:10.1371/journal.pone.0095103

Strong vaccine-induced CD8 T-cell responses have cytolytic function in a chimpanzee clearing HCV infection

PLoS One. 2014 Apr 16;9(4):e95103. doi: 10.1371/journal.pone.0095103. eCollection 2014.

Authors

Babs E Verstrepen¹, Ernst J Verschoor¹, Zahra C Fagrouch¹, Petra Mooij¹, Natasja G de Groot², Ronald E Bontrop², Willy M Bogers¹, Jonathan L Heeney³, Gerrit Koopman¹

Affiliations

¹ Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
² Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
³ Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.

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 NS3 1258-1272, 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
CD8-Positive T-Lymphocytes / drug effects*
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / virology
Cytokines / biosynthesis
Cytotoxicity, Immunologic / drug effects*
Epitopes / chemistry
Epitopes / immunology
Gene Expression
Hepacivirus / immunology*
Hepatitis C / immunology
Hepatitis C / prevention & control*
Hepatitis C / virology
Histocompatibility Antigens Class I / genetics
Histocompatibility Antigens Class I / immunology
Immunity, Cellular / drug effects
Immunity, Humoral / drug effects
Immunization
Molecular Sequence Data
Pan troglodytes
Viral Core Proteins / administration & dosage
Viral Core Proteins / genetics
Viral Core Proteins / immunology
Viral Hepatitis Vaccines / administration & dosage
Viral Hepatitis Vaccines / genetics
Viral Hepatitis Vaccines / immunology*
Viral Nonstructural Proteins / administration & dosage
Viral Nonstructural Proteins / genetics
Viral Nonstructural Proteins / immunology

Substances

Cytokines
Epitopes
Histocompatibility Antigens Class I
NS3 protein, hepatitis C virus
Viral Core Proteins
Viral Hepatitis Vaccines
Viral Nonstructural Proteins

Grants and funding

This research was initiated by EC grant number QLK2-CT-1999-00356 and supported by ZonMw number 114024014. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.