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Selecting the appropriate nanoparticle scaffold is crucial to controlling target antigens immunologically. Lumazine synthase (LS) is an attractive candidate for a vaccine display system due to its thermostability, modification tolerance, and morphological plasticity. Here, the first development of a multivalent thermostable scaffold, LS\u2010SUMO (SUMO, small ubiquitin\u2010likemodifier), and a divalent nanovaccine covalently conjugated with Chikungunya virus E2 and Zika virus EDIII antigens, is reported. Compared with antigen monomers, LS\u2010SUMO nanoparticle vaccines elicit a higher humoral response and neutralizing antibodies against both antigen targets in mouse sera. Mice immunized with LS\u2010SUMO conjugates produce CD4<jats:sup>+<\/jats:sup> T cell\u2010mediated Th2\u2010biased responses and promote humoral immunity. Importantly, LS\u2010SUMO conjugates possess equivalent humoral immunogenicity after heat treatment. Taken together, LS\u2010SUMO is a powerful biotargeting nanoplatform with high\u2010yield production, thermal stability and opens a new avenue for multivalent presentation of various antigens.<\/jats:p>","DOI":"10.1002\/adhm.202303619","type":"journal-article","created":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T07:58:51Z","timestamp":1707551931000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Divalent Chikungunya and Zika Nanovaccine with Thermostable Self\u2010Assembly Multivalent Scaffold LS\u2010SUMO"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6336-2715","authenticated-orcid":false,"given":"Qianlin","family":"Li","sequence":"first","affiliation":[{"name":"Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou 510080 China"},{"name":"One Health Center of Excellence for Research and Training School of Public Health Sun Yat\u2010sen University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Zhang","sequence":"additional","affiliation":[{"name":"One Health Center of Excellence for Research and Training School of Public Health Sun Yat\u2010sen University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Deng","sequence":"additional","affiliation":[{"name":"One Health Center of Excellence for Research and Training School of Public Health Sun Yat\u2010sen University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conghui","family":"Liao","sequence":"additional","affiliation":[{"name":"One Health Center of Excellence for Research and Training School of Public Health Sun Yat\u2010sen University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Qian","sequence":"additional","affiliation":[{"name":"Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeliang","family":"Chen","sequence":"additional","affiliation":[{"name":"One Health Center of Excellence for Research and Training School of Public Health Sun Yat\u2010sen University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahai","family":"Lu","sequence":"additional","affiliation":[{"name":"One Health Center of Excellence for Research and Training School of Public Health Sun Yat\u2010sen University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw2853"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01432"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2016.03.001"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4435"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8CS00154E"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2020.1760735"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac5894"},{"key":"e_1_2_9_8_1","first-page":"E690","volume":"12","author":"Zakeri B.","year":"2012","journal-title":"Proc. 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