{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:04:50Z","timestamp":1791453890512,"version":"4.3.3"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010771","name":"Bundesanstalt f\u00fcr Landwirtschaft und Ern\u00e4hrung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010771","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Vaccination is the best form of protecting fish against viral diseases when the pathogen cannot be contained by biosecurity measures. Vaccines based on live attenuated viruses seem to be most effective for vaccination against challenging pathogens like <jats:italic>Cyprinid herpesvirus 3<\/jats:italic>. However, there are still knowledge gaps how these vaccines effectively protect fish from the deadly disease caused by the epitheliotropic CyHV-3, and which aspects of non-direct protection of skin or gill integrity and function are important in the aquatic environment. To elucidate some elements of protection, common carp were vaccinated against CyHV-3 using a double deletion vaccine virus KHV-T \u0394DUT\/TK in the absence or presence of a mix of common carp beta-defensins 1, 2 and 3 as adjuvants. Vaccination induced marginal clinical signs, low virus load and a minor upregulation of <jats:italic>cd4<\/jats:italic>, <jats:italic>cd8<\/jats:italic> and <jats:italic>igm<\/jats:italic> gene expression in vaccinated fish, while neutralisation activity of blood serum rose from 14 days post vaccination (dpv). A challenge infection with CyHV-3 induced a severe disease with 80-100% mortality in non-vaccinated carp, while in vaccinated carp, no mortality was recorded and the virus load was &amp;gt;1,000-fold lower in the skin, gill and kidney. Histological analysis showed strongest pathological changes in the skin, with a complete destruction of the epidermis in non-vaccinated carp. In the skin of non-vaccinated fish, T and B cell responses were severely downregulated, inflammation and stress responses were increased upon challenge, whereas vaccinated fish had boosted neutrophil, T and B cell responses. A disruption of skin barrier elements (tight and adherence junction, desmosomes, mucins) led to an uncontrolled increase in skin bacteria load which most likely exacerbated the inflammation and the pathology. Using a live attenuated virus vaccine, we were able to show that increased neutrophil, T and B cell responses provide protection from CyHV-3 infection and lead to preservation of skin integrity, which supports successful protection against additional pathogens in the aquatic environment which foster disease development in non-vaccinated carp.<\/jats:p>","DOI":"10.3389\/fimmu.2022.787021","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T15:04:16Z","timestamp":1643641456000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Don\u2019t Let It Get Under Your Skin! \u2013 Vaccination Protects the Skin Barrier of Common Carp From Disruption Caused by Cyprinid Herpesvirus 3"],"prefix":"10.3389","volume":"13","author":[{"given":"Mikolaj","family":"Adamek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Matras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Rebl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Stachnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Falco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Carina","family":"Miebach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Teitge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Jung-Schroers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Abdullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben","family":"Krebs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Schr\u00f6der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Reichert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Steinhagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1111\/j.1600-065X.2011.01074.x","article-title":"Immune Modulation During Latent Herpesvirus Infection","volume":"245","author":"White","year":"2012","journal-title":"Immunol Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05762","article-title":"Herpesvirus Latency Confers Symbiotic Protection From Bacterial Infection","volume":"447","author":"Barton","year":"2007","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/v3112160","article-title":"Herpesviruses That Infect Fish","volume":"3","author":"Hanson","year":"2011","journal-title":"Viruses"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsi.2019.02.022","article-title":"Type I Interferon Responses of Common Carp Strains With Different Levels of Resistance to Koi Herpesvirus Disease During Infection With CyHV-3 or SVCV","volume":"87","author":"Adamek","year":"2019","journal-title":"Fish Shellfish Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00211-08","article-title":"Cloning of the Koi Herpesvirus Genome as an Infectious Bacterial Artificial Chromosome Demonstrates That Disruption of the Thymidine Kinase Locus Induces Partial Attenuation in Cyprinus Carpio Koi","volume":"82","author":"Costes","year":"2008","journal-title":"J Virol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1297-9716-43-6","article-title":"Feeding Cyprinus Carpio With Infectious Materials Mediates Cyprinid Herpesvirus 3 Entry Through Infection of Pharyngeal Periodontal Mucosa","volume":"43","author":"Fournier","year":"2012","journal-title":"Vet Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsi.2012.11.010","article-title":"Intestinal Barrier of Carp (Cyprinus Carpio L.) 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