{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:02:55Z","timestamp":1790949775403,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T00:00:00Z","timestamp":1586822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["211042\/Z\/18\/Z"],"award-info":[{"award-number":["211042\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Chronic hepatitis B virus (HBV) infection affects 257 million people globally. Current therapies suppress HBV but viral rebound occurs on cessation of therapy; novel therapeutic strategies are urgently required. To develop a therapeutic HBV vaccine that can induce high magnitude T cells to all major HBV antigens, we have developed a novel HBV vaccine using chimpanzee adenovirus (ChAd) and modified vaccinia Ankara (MVA) viral vectors encoding multiple HBV antigens. ChAd vaccine alone generated very high magnitude HBV specific T cell responses to all HBV major antigens. The inclusion of a shark Invariant (SIi) chain genetic adjuvant significantly enhanced the magnitude of T-cells against HBV antigens. Compared to ChAd alone vaccination, ChAd-prime followed by MVA-boost vaccination further enhanced the magnitude and breadth of the vaccine induced T cell response. Intra-cellular cytokine staining study showed that HBV specific CD8+ and CD4+ T cells were polyfunctional, producing combinations of IFN\u03b3, TNF-\u03b1, and IL-2. In summary, we have generated genetically adjuvanted ChAd and MVA vectored HBV vaccines with the potential to induce high-magnitude T cell responses through a prime-boost therapeutic vaccination approach. These pre-clinical studies pave the way for new studies of HBV therapeutic vaccination in humans with chronic hepatitis B infection.<\/jats:p>","DOI":"10.3390\/vaccines8020184","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T04:01:46Z","timestamp":1586923306000},"page":"184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4404-0229","authenticated-orcid":false,"given":"Senthil K.","family":"Chinnakannan","sequence":"first","affiliation":[{"name":"Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamsin N.","family":"Cargill","sequence":"additional","affiliation":[{"name":"Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Donnison","sequence":"additional","affiliation":[{"name":"Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Azim","family":"Ansari","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Sebastian","sequence":"additional","affiliation":[{"name":"Vaccitech, The Oxford Science Park, The Schrodinger Building, Heatley Road, Oxford OX4 4GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian Ni","family":"Lee","sequence":"additional","affiliation":[{"name":"Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Hutchings","sequence":"additional","affiliation":[{"name":"Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mala K.","family":"Maini","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London WC1E 6JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Evans","sequence":"additional","affiliation":[{"name":"Vaccitech, The Oxford Science Park, The Schrodinger Building, Heatley Road, Oxford OX4 4GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Barnes","sequence":"additional","affiliation":[{"name":"Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1053\/j.gastro.2014.01.044","article-title":"Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA","volume":"146","author":"Chan","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, M.R., Xi, H.L., Wang, Q.H., Hou, F.Q., Huo, N., Zhang, X.X., Li, F., and Xu, X.Y. 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