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Here we describe a set of therapeutic HBV vaccines that target the internal viral proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Vaccines are delivered by chimpanzee adenovirus vectors (AdC) of serotype 6 (AdC6) and 7 (AdC7) used in prime only or prime-boost regimens. The HBV antigens are fused into an early T cell checkpoint inhibitor, herpes simplex virus (HSV) glycoprotein D (gD), which enhances and broadens vaccine-induced cluster of differentiation (CD8)<jats:sup>+<\/jats:sup>T cell responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results show that the vaccines are immunogenic in mice. They induce potent CD8<jats:sup>+<\/jats:sup>T cell responses that recognize multiple epitopes. CD8<jats:sup>+<\/jats:sup>T cell responses increase after a boost, although the breadth remains similar. In mice, which carry high sustained loads of HBV particles due to a hepatic infection with an adeno-associated virus (AAV)8 vector expressing the 1.3HBV genome, CD8<jats:sup>+<\/jats:sup>T cell responses to the vaccines are attenuated with a marked shift in the CD8<jats:sup>+<\/jats:sup>T cells\u2019 epitope recognition profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data show that in different stains of mice including those that carry a human major histocompatibility complex (MHC) class I antigen HBV vaccines adjuvanted with a checkpoint inhibitor induce potent and broad HBV-specific CD8<jats:sup>+<\/jats:sup>T cell responses and lower but still detectable CD4<jats:sup>+<\/jats:sup>T cell responses. CD8<jats:sup>+<\/jats:sup>T cell responses are reduced and their epitope specificity changes in mice that are chronically exposed to HBV antigens. Implications for the design of therapeutic HBV vaccines are discussed.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12985-021-01712-y","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T11:02:33Z","timestamp":1638874953000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hepatitis B virus polymerase-specific T cell epitopes shift in a mouse model of chronic infection"],"prefix":"10.1186","volume":"18","author":[{"given":"Mohadeseh","family":"Hasanpourghadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Novikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dakota","family":"Newman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhiQuan","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang Yang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Magowan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9795-5206","authenticated-orcid":false,"given":"Hildegund C. 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Colin Magowan owns equity in Virion Therapeutics and is an inventor on a patent application covering, in part, the material in this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"242"}}