| Literature DB >> 32161099 |
Benjamin J Burwitz1,2, Patrick K Hashiguchi1, Mandana Mansouri1, Christine Meyer3, Roxanne M Gilbride1, Sreya Biswas1, Jennie L Womack1, Jason S Reed1, Helen L Wu1, Michael K Axthelm1,2, Scott G Hansen1,2, Louis J Picker1,2, Klaus Früh4,2, Jonah B Sacha4,2.
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, MHC-E-restricted CD8+ T cells from RM vaccinated with RM CMV vaccine vectors expressing HBV Ags 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.Entities:
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Year: 2020 PMID： 32161099 PMCID： PMC8109620 DOI： 10.4049/jimmunol.1900795
Source DB: PubMed Journal: J Immunol ISSN： 0022-1767 Impact factor: 5.422