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Genetic vaccines can be rapidly produced and could therefore mitigate pandemic outbreaks. Here, we present preclinical proof of protective efficacy of a DNA vaccine encoding a vaccine protein that targets influenza hemagglutinin (HA) to human leukocyte antigen class II (HLAII) molecules on antigen presenting cells (APC). Vaccination of mice raised robust levels of neutralizing antibodies, and protection against a lethal challenge with influenza H7N1 virus. In ferrets, we observed induction of neutralizing antibodies and T-cell responses after a single vaccination, with levels increasing after a second dose. Protection of vaccinated ferrets against a viral challenge with influenza H7N9 was dose dependent, with ferrets receiving the highest vaccine dose being completely protected from clinical disease. In sum, these results warrant progression to a human clinical Phase I trial.<\/jats:p>","DOI":"10.1038\/s41541-025-01341-4","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T06:35:41Z","timestamp":1766558141000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An HLAII-targeted DNA vaccine against influenza H7N9 protected mice and ferrets from a virus challenge"],"prefix":"10.1038","volume":"11","author":[{"given":"Rineke","family":"de Jong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tor Kristian","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Stockhofe-Zurwieden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca Jane","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjarne","family":"Bogen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnveig","family":"Grodeland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"1341_CR1","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/NEJMoa2035389","volume":"384","author":"LR Baden","year":"2021","unstructured":"Baden, L. 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BB is also an inventor on several Vaccibody-related patents (basis-patent, MIP-1\u03b1), and is a co-founder of the Nykode company and holds shares in the company. RJ, FZ, TKA, NSZ and RJC declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20"}}