Enhanced and sustained CD8+ T cell responses with an adenoviral vector-based hepatitis C virus vaccine encoding NS3 linked to the MHC class II chaperone protein invariant chain
Research output: Contribution to journal › Journal article › Research › peer-review
Potent and broad cellular immune responses against the nonstructural (NS) proteins of hepatitis C virus (HCV) are associated with spontaneous viral clearance. In this study, we have improved the immunogenicity of an adenovirus (Ad)-based HCV vaccine by fusing NS3 from HCV (Strain J4; Genotype 1b) to the MHC class II chaperone protein invariant chain (Ii). We found that, after a single vaccination of C57BL/6 or BALB/c mice with Ad-IiNS3, the HCV NS3-specific CD8(+) T cell responses were significantly enhanced, accelerated, and prolonged compared with the vaccine encoding NS3 alone. The AdIiNS3 vaccination induced polyfunctional CD8(+) T cells characterized by coproduction of IFN-¿, TNF-a and IL-2, and this cell phenotype is associated with good viral control. The memory CD8(+) T cells also expressed high levels of CD27 and CD127, which are markers of long-term survival and maintenance of T cell memory. Functionally, the AdIiNS3-vaccinated mice had a significantly increased cytotoxic capacity compared with the AdNS3 group. The AdIiNS3-induced CD8(+) T cells protected mice from infection with recombinant vaccinia virus expressing HCV NS3 of heterologous 1b strains, and studies in knockout mice demonstrated that this protection was mediated primarily through IFN-¿ production. On the basis of these promising results, we suggest that this vaccination technology should be evaluated further in the chimpanzee HCV challenge model.
Original language | English |
---|---|
Journal | Journal of Immunology |
Volume | 186 |
Issue number | 4 |
Pages (from-to) | 2355-64 |
Number of pages | 10 |
ISSN | 0022-1767 |
DOIs | |
Publication status | Published - 15 Feb 2011 |
- Adenoviridae, Animals, Antigens, CD27, Antigens, Differentiation, B-Lymphocyte, CD8-Positive T-Lymphocytes, Cell Survival, Cytotoxicity Tests, Immunologic, Disease Models, Animal, Epitopes, T-Lymphocyte, Female, Genetic Vectors, Hepacivirus, Hepatitis C, Histocompatibility Antigens Class II, Immunologic Memory, Immunophenotyping, Interleukin-7 Receptor alpha Subunit, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Recombinant Fusion Proteins, Vaccinia virus, Viral Hepatitis Vaccines, Viral Nonstructural Proteins
Research areas
ID: 33587302