{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:49:04Z","timestamp":1788569344435,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases","award":["75N93019C00052"],"award-info":[{"award-number":["75N93019C00052"]}]},{"name":"Georgia Research Alliance","award":["75N93019C00052"],"award-info":[{"award-number":["75N93019C00052"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The influenza neuraminidase (NA) is a promising target for next-generation vaccines. Protection induced by vaccination with the computationally optimized broadly reactive NA antigen (N1-I COBRA NA) was characterized in both influenza serologically naive and pre-immune ferret models following H1N1 (A\/California\/07\/2009, CA\/09) or H5N1 (A\/Vietnam\/1203\/2004, Viet\/04) influenza challenges. The N1-I COBRA NA vaccine elicited antibodies with neutralizing ELLA activity against both seasonal and pandemic H1N1 influenza, as well as the H5N1 influenza virus. In both models, N1-I COBRA NA-vaccinated ferrets that were challenged with CA\/09 virus had similar morbidity (weight loss and clinical symptoms) as ferrets vaccinated with the CA\/09 HA control vaccine. There were significantly reduced viral titers compared to the mock-vaccinated control animals. Ferrets vaccinated with N1-I COBRA NA or Viet\/04 NA vaccines were protected against the H5N1 virus infection with minimal clinical symptoms and negligible weight loss. In contrast, ferrets vaccinated with the CA\/09 NA vaccine lost ~10% of their original body weight with 25% mortality. Vaccination with either HA or NA vaccines did not inhibit contact transmission of CA\/09 virus to na\u00efve cage mates. Overall, the N1-I COBRA vaccine elicited protective immune responses against both H1N1 and H5N1 infections and partially mitigated disease in contact-transmission receiving ferrets. These results indicate that the N1-I COBRA NA performed similarly to the CA\/09 HA and NA positive controls. Therefore, the N1-I COBRA NA alone induces protection against viruses from both H5N1 and H1N1 subtypes, indicating its value as a vaccine component in broadly protective influenza vaccines.<\/jats:p>","DOI":"10.3390\/v15010184","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T02:31:30Z","timestamp":1673231490000},"page":"184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Multi-Influenza HA Subtype Protection of Ferrets Vaccinated with an N1 COBRA-Based Neuraminidase"],"prefix":"10.3390","volume":"15","author":[{"given":"Amanda L.","family":"Skarlupka","sequence":"first","affiliation":[{"name":"Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8706-3156","authenticated-orcid":false,"given":"Xiaojian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4505-8305","authenticated-orcid":false,"given":"Uriel","family":"Blas-Machado","sequence":"additional","affiliation":[{"name":"Athens Veterinary Diagnostic Laboratory, University of Georgia, Athens, GA 30602, USA"},{"name":"Department of Pathology, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer F.","family":"Sumner","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted M.","family":"Ross","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA"},{"name":"Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA"},{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA"},{"name":"Department of Infection Biology, Lehner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1093\/infdis\/jiaa105","article-title":"Avian Influenza Human Infections at the Human-Animal Interface","volume":"222","author":"Philippon","year":"2020","journal-title":"J. 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