{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T12:11:36Z","timestamp":1774008696004,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union Horizon Europe Programme","award":["101137459"],"award-info":[{"award-number":["101137459"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Chimpanzee adenoviral-vectored vaccines have proven to be both safe and effective, with a manufacturing and distribution pipeline capable of rapid global supply, as demonstrated during the COVID-19 pandemic. Yellow fever is a mosquito-borne viral hemorrhagic disease endemic in parts of Africa and Latin America, and although an effective live attenuated vaccine exists, its use is limited by safety and eligibility restrictions. Moreover, large outbreaks continue to expose critical challenges, such as an insufficient vaccine supply, reliance on fractional dosing, and slow and difficult-to-scale manufacturing processes. Here, we report the design, development and in vivo immunogenicity of multiple yellow fever virus (YFV) antigen constructs based on the pre-membrane (prM) and envelope (E) proteins\u2014with or without the transmembrane domain (TM or \u0394TM)\u2014delivered using the ChAdOx1 adenoviral vector. Methods: Four ChAdOx1 YF vaccines were developed, and immunogenicity was evaluated. The efficacy of the full-length YF envelope vaccine was also tested in Balb\/c mice. Results\/Conclusions: In contrast to previously described orthoflavivirus vaccines on the same platform, the full-length antigen elicited superior immunogenicity and conferred protection against intracranial challenge with the YF17D virus in mice. Notably, this protection was comparable to that induced by the licensed YF17D vaccine, highlighting the promise of this platform as a next-generation yellow fever vaccine candidate.<\/jats:p>","DOI":"10.3390\/vaccines14030273","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T09:44:41Z","timestamp":1773999881000},"page":"273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rational Design of a Chimpanzee Adenoviral-Vector Vaccine Against Yellow Fever Through the Modification of Antigen Transmembrane Domains"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4288-2892","authenticated-orcid":false,"given":"Marta","family":"Ulaszewska","sequence":"first","affiliation":[{"name":"Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7TY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji","family":"Ma","sequence":"additional","affiliation":[{"name":"Virology, Antiviral Drug & Vaccine Research Group, Laboratory of Molecular Vaccinology and Vaccine Discovery (MVVD), KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1813-0557","authenticated-orcid":false,"given":"Susan J.","family":"Morris","sequence":"additional","affiliation":[{"name":"Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7TY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4584-814X","authenticated-orcid":false,"given":"Sophie M.","family":"Jegouic Goodall","sequence":"additional","affiliation":[{"name":"Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7TY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4933-6448","authenticated-orcid":false,"given":"Winnie","family":"Kerstens","sequence":"additional","affiliation":[{"name":"Virology, Antiviral Drug & Vaccine Research Group, Translational Platform for Virus, Vaccine and Cancer Research (TPVC), KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute,  3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5785-8276","authenticated-orcid":false,"given":"Hendrik Jan","family":"Thibaut","sequence":"additional","affiliation":[{"name":"Virology, Antiviral Drug & Vaccine Research Group, Translational Platform for Virus, Vaccine and Cancer Research (TPVC), KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute,  3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7888-4534","authenticated-orcid":false,"given":"Lotte","family":"Coelmont","sequence":"additional","affiliation":[{"name":"Virology, Antiviral Drug & Vaccine Research Group, Laboratory of Molecular Vaccinology and Vaccine Discovery (MVVD), KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8117-9166","authenticated-orcid":false,"given":"Kai","family":"Dallmeier","sequence":"additional","affiliation":[{"name":"Virology, Antiviral Drug & Vaccine Research Group, Laboratory of Molecular Vaccinology and Vaccine Discovery (MVVD), KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6823-9750","authenticated-orcid":false,"given":"Sarah C.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7TY, UK"},{"name":"CAMS Oxford Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, University of Oxford, Oxford OX3 7BN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1692-9987","authenticated-orcid":false,"given":"Barbara","family":"Dema","sequence":"additional","affiliation":[{"name":"Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7TY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10842","DOI":"10.1038\/s41598-024-60680-9","article-title":"Advancing molecular modeling and reverse vaccinology in broad-spectrum yellow fever virus vaccine development","volume":"14","author":"Manzoni","year":"2024","journal-title":"Sci. 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