{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T02:18:49Z","timestamp":1789265929292,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"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":"National Institute of Allergy and Infectious Diseases","award":["GRA-001"],"award-info":[{"award-number":["GRA-001"]}]},{"name":"Georgia Research Alliance","award":["75N93019C00052"],"award-info":[{"award-number":["75N93019C00052"]}]},{"name":"Georgia Research Alliance","award":["GRA-001"],"award-info":[{"award-number":["GRA-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Standard-of-care influenza vaccines contain antigens that are typically derived from components of wild type (WT) influenza viruses. Often, these antigens elicit strain-specific immune responses and are susceptible to mismatch in seasons where antigenic drift is prevalent. Thanks to advances in viral surveillance and sequencing, influenza vaccine antigens can now be optimized using computationally derived methodologies and algorithms to enhance their immunogenicity. Methods: Mice and ferrets that had been previously exposed to historical H1N1 and H3N2 influenza viruses were vaccinated intramuscularly with bivalent mixtures of H1 and H3 recombinant hemagglutinin (rHA) proteins, which were generated using a computationally optimized broadly reactive antigen (COBRA) design methodology. The vaccine antigens were mixed with a cationic lipid nanoparticle adjuvant, Infectimune\u00ae, which promotes both humoral and cellular immune responses. Results: Mice and ferrets vaccinated with Infectimune\u00ae and COBRA rHAs elicited protective antibody titers against panels of H1N1 and H3N2 influenza viruses isolated over the past 10 years. These animals also had antibodies that neutralized numerous modern H1N1 and H3N2 influenza viruses in vitro. When challenged with the A\/Victoria\/2570\/2019 H1N1 influenza virus, the COBRA rHA vaccinated animals had minimal weight loss, and no detectable virus was present in their respiratory tissues on day 3 post-infection. Conclusions: These results demonstrate that COBRA rHA vaccines formulated with Infectimune\u00ae elicit protective antibody responses against influenza strains, which were isolated across periods of time when standard-of-care vaccines were frequently reformulated, thus reducing the need to update vaccines on a nearly annual basis.<\/jats:p>","DOI":"10.3390\/vaccines12121364","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T13:34:04Z","timestamp":1733146444000},"page":"1364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Computationally Optimized Hemagglutinin Proteins Adjuvanted with Infectimune\u00ae Generate Broadly Protective Antibody Responses in Mice and Ferrets"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3798-706X","authenticated-orcid":false,"given":"James D.","family":"Allen","sequence":"first","affiliation":[{"name":"Center for Vaccines and Immunology, University of Georgia, Athens, GA 30605, USA"},{"name":"Department of Infectious Diseases, University of Georgia, Athens, GA 30605, USA"},{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, 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 30605, USA"},{"name":"Department of Infectious Diseases, University of Georgia, Athens, GA 30605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Medina","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9785-9413","authenticated-orcid":false,"given":"Matthew H.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5210-9563","authenticated-orcid":false,"given":"Amanda","family":"Lynch","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Nelson","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Aguirre","sequence":"additional","affiliation":[{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1947-7469","authenticated-orcid":false,"given":"Ted M.","family":"Ross","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunology, University of Georgia, Athens, GA 30605, USA"},{"name":"Department of Infectious Diseases, University of Georgia, Athens, GA 30605, USA"},{"name":"Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA"},{"name":"Department of Infection Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"ref_1","first-page":"2","article-title":"The societal and indirect economic burden of seasonal influenza in the United Kingdom","volume":"10","author":"Romanelli","year":"2023","journal-title":"Rand Health Q."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Postma, M., Fisman, D., Giglio, N., M\u00e1rquez-Pel\u00e1ez, S., Nguyen, V.H., Pugliese, A., Ruiz-Arag\u00f3n, J., Urue\u00f1a, A., and Mould-Quevedo, J. 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