{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:13:28Z","timestamp":1786119208443,"version":"build-2736575974"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100031580","name":"National Vaccine Institute","doi-asserted-by":"crossref","award":["National Vaccine Institute, Grant No. 2567.1\/27"],"award-info":[{"award-number":["National Vaccine Institute, Grant No. 2567.1\/27"]}],"id":[{"id":"10.13039\/100031580","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004776","name":"Faculty of Medicine, Chulalongkorn University","doi-asserted-by":"crossref","award":["the Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University,RA-MF-26\/68"],"award-info":[{"award-number":["the Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University,RA-MF-26\/68"]}],"id":[{"id":"10.13039\/501100004776","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Dengue virus (DENV) remains a major global health burden, with four antigenically distinct serotypes (DENV-1\u20134) posing a significant challenge for vaccine development. Dengue non-structural protein 1 (NS1) has been associated with additional protection and reduced disease severity, supporting its inclusion in vaccine design. In this study, we designed a consensus NS1 (cNS1) antigen by integrating sequence elements from all four DENV serotypes (78\u201389% amino acid identity) to enhance cross-serotype antigenic coverage. The cNS1 sequence was encoded as a nucleoside-modified mRNA and formulated in lipid nanoparticles (mRNA\u2013LNPs). Immunization of BALB\/c mice with a low dose (0.2 \u00b5g) of cNS1 mRNA\u2013LNP induced broadly reactive NS1-specific IgG responses that recognized NS1 proteins from all four serotypes. In addition, the vaccine elicited interferon-\u03b3 (IFN-\u03b3)\u2013producing T cell responses against peptide pools derived from multiple DENV serotypes, indicating the activation of cross-reactive cellular immunity. While broad immune recognition was achieved, this was accompanied by lower serotype-specific response magnitudes as a trade-off. In conclusion, the cNS1 mRNA vaccine induces cross-serotype humoral and cellular immune responses in mice, highlighting the potential of consensus antigen design to broaden immune recognition of DENV NS1. These findings support the further development of NS1-based immunogens as complementary components of next-generation dengue vaccines aimed at achieving broad and effective protection.<\/jats:p>","DOI":"10.1371\/journal.pone.0355389","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T17:44:44Z","timestamp":1786038284000},"page":"e0355389","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross-serotype immunity elicited by a consensus dengue NS1 mRNA vaccine in mice"],"prefix":"10.1371","volume":"21","author":[{"given":"Kittipan","family":"Tharakhet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eakachai","family":"Prompetchara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chirayus","family":"Khawsang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supichcha","family":"Saithong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Papatsara","family":"Kaewpang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nongnaphat","family":"Yostrerat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6162-724X","authenticated-orcid":true,"given":"Pachara","family":"Wangsoontorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenjira","family":"Sontikun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawaros","family":"Tantratorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thidarat","family":"Khotprathum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieu","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Heyes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drew","family":"Weissman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiat","family":"Ruxrungtham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7043-8062","authenticated-orcid":true,"given":"Chutitorn","family":"Ketloy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"pone.0355389.ref001","volume-title":"Dengue and severe dengue","author":"WH Organization","year":"2024"},{"key":"pone.0355389.ref002","doi-asserted-by":"crossref","first-page":"16055","DOI":"10.1038\/nrdp.2016.55","article-title":"Dengue infection","volume":"2","author":"MG Guzman","year":"2016","journal-title":"Nat Rev Dis Primers"},{"issue":"15","key":"pone.0355389.ref003","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1056\/NEJMra1110265","article-title":"Dengue","volume":"366","author":"CP Simmons","year":"2012","journal-title":"N Engl J Med"},{"issue":"7446","key":"pone.0355389.ref004","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"S Bhatt","year":"2013","journal-title":"Nature"},{"issue":"6","key":"pone.0355389.ref005","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/S1473-3099(16)00026-8","article-title":"The global burden of dengue: an analysis from the Global Burden of Disease Study 2013","volume":"16","author":"JD Stanaway","year":"2016","journal-title":"Lancet Infect Dis"},{"issue":"13","key":"pone.0355389.ref006","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1056\/NEJMoa1506223","article-title":"Efficacy and long-term safety of a dengue vaccine in regions of endemic disease","volume":"373","author":"SR Hadinegoro","year":"2015","journal-title":"N Engl J Med"},{"issue":"21","key":"pone.0355389.ref007","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1056\/NEJMoa1903869","article-title":"Efficacy of a tetravalent dengue vaccine in healthy children and adolescents","volume":"381","author":"S Biswal","year":"2019","journal-title":"N Engl J Med"},{"issue":"6365","key":"pone.0355389.ref008","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1126\/science.aan6836","article-title":"Antibody-dependent enhancement of severe dengue disease in humans","volume":"358","author":"LC Katzelnick","year":"2017","journal-title":"Science"},{"issue":"47","key":"pone.0355389.ref009","doi-asserted-by":"crossref","first-page":"6355","DOI":"10.1016\/j.vaccine.2017.09.089","article-title":"Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age","volume":"35","author":"SB Halstead","year":"2017","journal-title":"Vaccine"},{"issue":"304","key":"pone.0355389.ref010","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaa3863","article-title":"Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity","volume":"7","author":"N Modhiran","year":"2015","journal-title":"Sci Transl Med"},{"issue":"6","key":"pone.0355389.ref011","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1016\/j.celrep.2019.01.036","article-title":"Flavivirus NS1 triggers tissue-specific vascular endothelial dysfunction reflecting disease tropism","volume":"26","author":"H Puerta-Guardo","year":"2019","journal-title":"Cell Rep"},{"issue":"11","key":"pone.0355389.ref012","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1006673","article-title":"Dengue virus NS1 cytokine-independent vascular leak is dependent on endothelial glycocalyx components","volume":"13","author":"DR Glasner","year":"2017","journal-title":"PLoS Pathog"},{"issue":"304","key":"pone.0355389.ref013","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaa3787","article-title":"Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination","volume":"7","author":"PR Beatty","year":"2015","journal-title":"Sci Transl Med"},{"issue":"3","key":"pone.0355389.ref014","article-title":"Protection against dengue virus infection in mice by administration of antibodies against modified nonstructural protein 1","volume":"9","author":"S-W Wan","year":"2014","journal-title":"PLoS One"},{"issue":"2","key":"pone.0355389.ref015","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.virol.2006.08.052","article-title":"DNA vaccines against dengue virus based on the ns1 gene: the influence of different signal sequences on the protein expression and its correlation to the immune response elicited in mice","volume":"358","author":"SM Costa","year":"2007","journal-title":"Virology"},{"issue":"2","key":"pone.0355389.ref016","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/sj.mt.6300036","article-title":"Enhanced cellular immune responses elicited by an engineered HIV-1 subtype B consensus-based envelope DNA vaccine","volume":"15","author":"J Yan","year":"2007","journal-title":"Mol Ther"},{"key":"pone.0355389.ref017","article-title":"Centralized immunogens as a vaccine strategy to overcome HIV-1 diversity","volume":"3","author":"F Gao","year":"2004","journal-title":"Expert Rev Vaccines"},{"issue":"4","key":"pone.0355389.ref018","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrd.2017.243","article-title":"mRNA vaccines - a new era in vaccinology","volume":"17","author":"N Pardi","year":"2018","journal-title":"Nat Rev Drug Discov"},{"issue":"10","key":"pone.0355389.ref019","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrd4278","article-title":"mRNA-based therapeutics--developing a new class of drugs","volume":"13","author":"U Sahin","year":"2014","journal-title":"Nat Rev Drug Discov"},{"issue":"12","key":"pone.0355389.ref020","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","article-title":"Lipid nanoparticles for mRNA delivery","volume":"6","author":"X Hou","year":"2021","journal-title":"Nat Rev Mater"},{"issue":"6","key":"pone.0355389.ref021","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.cell.2017.02.017","article-title":"Modified mRNA vaccines protect against Zika virus infection","volume":"168","author":"JM Richner","year":"2017","journal-title":"Cell"},{"key":"pone.0355389.ref022","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.omtm.2020.07.013","article-title":"Modified mRNA-LNP vaccines confer protection against experimental DENV-2 infection in mice","volume":"18","author":"M Zhang","year":"2020","journal-title":"Mol Ther Methods Clin Dev"},{"key":"pone.0355389.ref023","article-title":"Identifying candidate targets of immune responses in Zika virus based on homology to epitopes in other Flavivirus species","volume":"8","author":"X Xu","year":"2016","journal-title":"PLoS Curr"},{"issue":"6173","key":"pone.0355389.ref024","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1126\/science.1247749","article-title":"Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system","volume":"343","author":"DL Akey","year":"2014","journal-title":"Science"},{"key":"pone.0355389.ref025","doi-asserted-by":"crossref","first-page":"128147","DOI":"10.1016\/j.vaccine.2025.128147","article-title":"Engineered dengue virus NS1 mRNA-lipid nanoparticle induces therapeutic IgG production that lacks autoantibody activity and neutralizes NS1 entry in liver cells","volume":"73","author":"S Das","year":"2026","journal-title":"Vaccine"},{"key":"pone.0355389.ref026","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.3389\/fimmu.2019.01778","article-title":"Assessing the diversity and stability of cellular immunity generated in response to the candidate live-attenuated dengue virus vaccine TAK-003","volume":"10","author":"AT Waickman","year":"2019","journal-title":"Front Immunol"},{"issue":"4","key":"pone.0355389.ref027","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1586\/14760584.2016.1128328","article-title":"A recombinant, chimeric tetravalent dengue vaccine candidate based on a dengue virus serotype 2 backbone","volume":"15","author":"JE Osorio","year":"2016","journal-title":"Expert Rev Vaccines"},{"key":"pone.0355389.ref028","doi-asserted-by":"crossref","first-page":"118485","DOI":"10.1016\/j.biopha.2025.118485","article-title":"A consensus HA DNA vaccine targeting clade 2.3.4.4 H5Nx influenza viruses provides broad cross-clade protection in mice and ferrets","volume":"191","author":"C-U Kim","year":"2025","journal-title":"Biomed Pharmacother"},{"issue":"2","key":"pone.0355389.ref029","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.virol.2011.02.022","article-title":"N-linked glycosylation of dengue virus NS1 protein modulates secretion, cell-surface expression, hexamer stability, and interactions with human complement","volume":"413","author":"P Somnuke","year":"2011","journal-title":"Virology"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355389","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T17:44:51Z","timestamp":1786038291000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355389"}},"subtitle":[],"editor":[{"given":"Julian","family":"Ruiz-Saenz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":29,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0355389","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,6]]}}}