{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:45:19Z","timestamp":1793825119884,"version":"4.6.1"},"reference-count":77,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Nebraska\u2013Lincoln (AKP)","award":["P20 GM113126"],"award-info":[{"award-number":["P20 GM113126"]}],"id":[{"id":"https:\/\/ror.org\/043mer456","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Nebraska\u2013Lincoln (AKP)","award":["P30CA036727"],"award-info":[{"award-number":["P30CA036727"]}],"id":[{"id":"https:\/\/ror.org\/043mer456","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Nebraska Center for Integrated Biomolecular Communication","award":["P20 GM113126"],"award-info":[{"award-number":["P20 GM113126"]}],"id":[{"id":"https:\/\/ror.org\/02vajdy81","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Nebraska Center for Integrated Biomolecular Communication","award":["P30CA036727"],"award-info":[{"award-number":["P30CA036727"]}],"id":[{"id":"https:\/\/ror.org\/02vajdy81","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM113126"],"award-info":[{"award-number":["P20 GM113126"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30CA036727"],"award-info":[{"award-number":["P30CA036727"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nebraska Agricultural Experiment Station","award":["P20 GM113126"],"award-info":[{"award-number":["P20 GM113126"]}]},{"name":"Nebraska Agricultural Experiment Station","award":["P30CA036727"],"award-info":[{"award-number":["P30CA036727"]}]},{"name":"Agricultural Research Division","award":["P20 GM113126"],"award-info":[{"award-number":["P20 GM113126"]}]},{"name":"Agricultural Research Division","award":["P30CA036727"],"award-info":[{"award-number":["P30CA036727"]}]},{"name":"Fred and Pamela Buffett NCI Cancer Center","award":["P20 GM113126"],"award-info":[{"award-number":["P20 GM113126"]}]},{"name":"Fred and Pamela Buffett NCI Cancer Center","award":["P30CA036727"],"award-info":[{"award-number":["P30CA036727"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>The severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain\u2013Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV infection. Herein, we describe the development of a bacterial ferritin-based nanoparticle vaccine candidate for ZIKV. The viral envelope (E) protein domain III (DIII) was fused in-frame at the amino-terminus of ferritin. The resulting nanoparticle displaying the DIII was examined for its ability to induce immune responses and protect vaccinated animals upon lethal virus challenge. Our results show that immunization of mice with a single dose of the nanoparticle vaccine candidate (zDIII-F) resulted in the robust induction of neutralizing antibody responses that protected the animals from the lethal ZIKV challenge. The antibodies neutralized infectivity of other ZIKV lineages indicating that the zDIII-F can confer heterologous protection. The vaccine candidate also induced a significantly higher frequency of interferon (IFN)-\u03b3 positive CD4 T cells and CD8 T cells suggesting that both humoral and cell-mediated immune responses were induced by the vaccine candidate. Although our studies showed that a soluble DIII vaccine candidate could also induce humoral and cell-mediated immunity and protect from lethal ZIKV challenge, the immune responses and protection conferred by the nanoparticle vaccine candidate were superior. Further, passive transfer of neutralizing antibodies from the vaccinated animals to na\u00efve animals protected against lethal ZIKV challenge. Since previous studies have shown that antibodies directed at the DIII region of the E protein do not to induce antibody-dependent enhancement (ADE) of ZIKV or other related flavivirus infections, our studies support the use of the zDIII-F nanoparticle vaccine candidate for safe and enhanced immunological responses against ZIKV.<\/jats:p>","DOI":"10.3390\/vaccines11040821","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T05:59:33Z","timestamp":1681106373000},"page":"821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus Challenge"],"prefix":"10.3390","volume":"11","author":[{"given":"Aryamav","family":"Pattnaik","sequence":"first","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bikash R.","family":"Sahoo","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas R.","family":"Struble","sequence":"additional","affiliation":[{"name":"The Eppley Institute for Cancer and Allied Diseases, Fred & Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8070-0258","authenticated-orcid":false,"given":"Gloria E. O.","family":"Borgstahl","sequence":"additional","affiliation":[{"name":"The Eppley Institute for Cancer and Allied Diseases, Fred & Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3241-8615","authenticated-orcid":false,"given":"Rodrigo","family":"Franco","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul G.","family":"Barletta","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando A.","family":"Osorio","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6163-4854","authenticated-orcid":false,"given":"Thomas M.","family":"Petro","sequence":"additional","affiliation":[{"name":"Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Department of Oral Biology, University of Nebraska Medical Center, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9581-6787","authenticated-orcid":false,"given":"Asit K.","family":"Pattnaik","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"},{"name":"Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/nrmicro.2016.125","article-title":"Zika virus\u2014Reigniting the TORCH","volume":"14","author":"Coyne","year":"2016","journal-title":"Nat. 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