{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:04:50Z","timestamp":1785524690901,"version":"3.56.0"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Current dengue vaccines remain limited by serotype\u2010dependent efficacy and interference from preexisting anti\u2010dengue immunity. We developed a novel multivalent fusion protein vaccine composed of three engineered dengue virus (DENV) components: a C\u2010terminal truncated nonstructural protein 1 (\u0394cNS1) to block NS1\u2010mediated pathologic effects without harmful cross\u2010reactivity, a consensus envelope protein domain III (cEDIII) to induce broad neutralizing antibodies, and an N\u2010terminal truncated NS3 (\u0394nNS3) to enhance cellular immune responses. In a murine dengue disease model, three\u2010dose immunization with \u0394cNS1\u2013cEDIII\u2013\u0394nNS3 adjuvanted with Alum provides protection against all four DENV serotypes by significantly reducing viremia and prolonged bleeding time, with elicited robust antibody responses, enhanced cytotoxic activity of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells upon NS1\/NS3 restimulation, and increased memory B and T cell populations. Notably, CpG oligodeoxynucleotides 1826 (CpG) plus Alum further enhanced immunogenicity, showing higher neutralizing activity, antigen\u2010specific plasmablast expansion, and enhanced T cell functional activity, which was associated with more consistent improvement in protection\u2010relevant outcomes compared with Alum alone. Importantly, two\u2010dose immunization with CpG plus Alum\u2010adjuvanted fusion protein conferred durable protection against the virulent DENV2 strain TW2015. These findings support this vaccine as a promising subunit candidate that addresses current limitations, offering both cross\u2010serotype coverage and potential long\u2010term efficacy.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70822","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T11:48:37Z","timestamp":1769860117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Multivalent Dengue Fusion Protein \u0394cNS1\u2013cEDIII\u2013\u0394nNS3 Confers Cross\u2010Serotype Protection and Durable Immunity in Mice"],"prefix":"10.1002","volume":"98","author":[{"given":"Mu\u2010Fan","family":"Pi","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Chiao","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Institute of Basic Medical Sciences, College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao\u2010Huei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu\u2010En","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Institute of Basic Medical Sciences, College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen\u2010Chung","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Leadgene Biomedical, Inc. Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsing\u2010Han","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"SIDSCO Biomedical Co. Ltd. Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung\u2010Chun","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Leadgene Biomedical, Inc. Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin\u2010Kai","family":"Tseng","sequence":"additional","affiliation":[{"name":"SIDSCO Biomedical Co. Ltd. Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee\u2010Shin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Peng","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Institute of Basic Medical Sciences, College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Center of Infectious Disease and Signaling Research National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzong\u2010Shiann","family":"Ho","sequence":"additional","affiliation":[{"name":"Center of Infectious Disease and Signaling Research National Cheng Kung University Tainan 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