{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:00:36Z","timestamp":1760148036820,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["398066876\/GRK 2485\/1","491094227"],"award-info":[{"award-number":["398066876\/GRK 2485\/1","491094227"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alexander von Humboldt Foundation","award":["398066876\/GRK 2485\/1","491094227"],"award-info":[{"award-number":["398066876\/GRK 2485\/1","491094227"]}]},{"name":"University of Veterinary Medicine Hannover, Foundation","award":["398066876\/GRK 2485\/1","491094227"],"award-info":[{"award-number":["398066876\/GRK 2485\/1","491094227"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>The four serotypes of dengue virus (DENV1\u20134) continue to pose a major public health threat. The first licenced dengue vaccine, which expresses the surface proteins of DENV1\u20134, has performed poorly in immunologically na\u00efve individuals, sensitising them to antibody-enhanced dengue disease. DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development. However, the intrinsic ability of NS1 to trigger vascular leakage is a potential drawback of its use as a vaccine antigen. Here, we modified DENV2 NS1 by mutating an N-linked glycosylation site associated with NS1-induced endothelial hyperpermeability and used modified vaccinia virus Ankara (MVA) as a vector for its delivery. The resulting construct, rMVA-D2-NS1-N207Q, displayed high genetic stability and drove efficient secretion of NS1-N207Q from infected cells. Secreted NS1-N207Q was composed of dimers and lacked N-linked glycosylation at position 207. Prime\u2013boost immunisation of C57BL\/6J mice induced high levels of NS1-specific antibodies binding various conformations of NS1 and elicited NS1-specific CD4+ T-cell responses. Our findings support rMVA-D2-NS1-N207Q as a promising and potentially safer alternative to existing NS1-based vaccine candidates, warranting further pre-clinical testing in a relevant mouse model of DENV infection.<\/jats:p>","DOI":"10.3390\/vaccines11040714","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T03:07:57Z","timestamp":1679540877000},"page":"714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5678-3089","authenticated-orcid":false,"given":"Lucas","family":"Wilken","sequence":"first","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine (TiHo), 30559 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8804-9092","authenticated-orcid":false,"given":"Sonja","family":"Stelz","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine (TiHo), 30559 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayse","family":"Agac","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine (TiHo), 30559 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6143-082X","authenticated-orcid":false,"given":"Gerd","family":"Sutter","sequence":"additional","affiliation":[{"name":"Division of Virology, Institute for Infectious Diseases and Zoonoses, Department of Veterinary Sciences, Ludwig Maximilian University (LMU), 80539 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6631-2096","authenticated-orcid":false,"given":"Chittappen Kandiyil","family":"Prajeeth","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine (TiHo), 30559 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1921-4581","authenticated-orcid":false,"given":"Guus F.","family":"Rimmelzwaan","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine (TiHo), 30559 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1128\/CMR.00035-09","article-title":"Dengue Virus Pathogenesis: An Integrated View","volume":"22","author":"Martina","year":"2009","journal-title":"Clin. 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