{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:09:20Z","timestamp":1780582160200,"version":"3.54.1"},"reference-count":97,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T00:00:00Z","timestamp":1398124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>West Nile virus (WNV) causes potentially fatal neuroinvasive disease and persists at endemic levels in many parts of the world. Despite advances in our understanding of WNV pathogenesis, there remains a significant need for a human vaccine. The domain III (DIII) region of the WNV envelope protein contains epitopes that are the target of neutralizing antibodies. We have constructed a chimeric fusion of the non-toxic cholera toxin (CT) CTA2\/B domains to DIII for investigation as a novel mucosally-delivered WNV vaccine. Purification and assembly of the chimera, as well as receptor-binding and antigen delivery, were verified by western blot, GM1 ELISA and confocal microscopy. Groups of BALB\/c mice were immunized intranasally with DIII-CTA2\/B, DIII, DIII mixed with CTA2\/B, or CTA2\/B control, and boosted at 10 days. Analysis of serum IgG after 14 and 45 days revealed that mucosal immunization with DIII-CTA2\/B induced significant DIII-specific humoral immunity and drove isotype switching to IgG2a. The DIII-CTA2\/B chimera also induced antigen-specific IgM and IgA responses. Bactericidal assays indicate that the DIII-CTA2\/B immunized mice produced DIII-specific antibodies that can trigger complement-mediated killing. A dose escalation resulted in increased DIII-specific serum IgG titers on day 45. DIII antigen alone, in the absence of adjuvant, also induced significant systemic responses after intranasal delivery. Our results indicate that the DIII-CTA2\/B chimera is immunogenic after intranasal delivery and merits further investigation as a novel WNV vaccine candidate.<\/jats:p>","DOI":"10.3390\/toxins6041397","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T12:18:37Z","timestamp":1398169117000},"page":"1397-1418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Immunogenicity of a West Nile Virus DIII-Cholera Toxin A2\/B Chimera after Intranasal Delivery"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8954-5810","authenticated-orcid":false,"given":"Juliette","family":"Tinker","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Boise State University, Boise, ID  83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reece","family":"Knippel","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Boise State University, Boise, ID  83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panos","family":"Panayiotou","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Boise State University, Boise, ID  83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Cornell","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Boise State University, Boise, ID  83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.4269\/ajtmh.1940.s1-20.471","article-title":"A neuotropic virus isolated from the blood of a native of Uganda","volume":"20","author":"Smithburn","year":"1940","journal-title":"Am. 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