Abstract
Currently 247 million people are living with chronic hepatitis B virus infection (CHB), and the development of novel curative treatments is urgently needed. Immunotherapy is an attractive approach to treat CHB, yet therapeutic approaches to augment the endogenous hepatitis B virus (HBV)-specific T cell response in CHB patients have demonstrated little success. In this study, we show that strain 68-1 rhesus macaque (RM) CMV vaccine vectors expressing HBV Ags engender HBV-specific CD8+ T cells unconventionally restricted by MHC class II and the nonclassical MHC-E molecule in RM. Surface staining of human donor and RM primary hepatocytes (PH) ex vivo revealed the majority of PH expressed MHC-E but not MHC class II. HBV-specific, MHCE- restricted CD8+ T cells from RM vaccinated with RM CMV vaccine vectors expressing HBVAgs recognized HBV-infected PH from both human donor and RM. These results provide proof-of-concept that MHC-E-restricted CD8+ T cells could be harnessed for the treatment of CHB, either through therapeutic vaccination or adoptive immunotherapy.
Original language | English (US) |
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Pages (from-to) | 2169-2176 |
Number of pages | 8 |
Journal | Journal of Immunology |
Volume | 204 |
Issue number | 8 |
DOIs | |
State | Published - Apr 15 2020 |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology