{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T21:31:27Z","timestamp":1769117487967,"version":"3.49.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    SARS-CoV-2 evolution, particularly the emergence of Omicron variants, has challenged vaccine efficacy, necessitating antigens with broad and variant-specific protection. To design mRNA vaccine antigens with broad-spectrum immunity and enhanced stability, we developed two spike antigens using\n                    <jats:italic>in silico<\/jats:italic>\n                    optimization: Css_dsg S, the ancestral strain\u2013Delta variant consensus with stabilizing mutations, and Omi_dsg S, an Omicron-adapted design. Computational analysis identified two critical N-terminal domain stabilization sites consistently enhancing protein expression across variants, suggesting their potential as universal stabilizing elements. Css_dsg S elicited robust IFN-\u03b3 T cell responses and significantly elevated neutralizing antibody titers against variants in BALB\/c mice. Omi_dsg S induced strong immune responses\n                    <jats:italic>in vivo<\/jats:italic>\n                    . A bivalent mRNA vaccine combining both antigens elicited superior neutralizing antibody responses and conferred enhanced protection against BN.1 and BA.5 challenges in K18-hACE2 mice. These findings support computationally optimized spike antigens, particularly the bivalent formulation, as a promising strategy for next-generation vaccines against SARS-CoV-2 variants.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1718740","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T05:15:00Z","timestamp":1769058900000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure-guided design of a bivalent SARS-CoV-2 mRNA vaccine with NTD stabilizing mutations enhances broad immunity"],"prefix":"10.3389","volume":"16","author":[{"given":"Jinah","family":"Yeo","sequence":"first","affiliation":[{"name":"Division of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency","place":["Cheongju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi-ran","family":"Yun","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency","place":["Cheongju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seo-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency","place":["Cheongju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Hyun","family":"Seok","sequence":"additional","affiliation":[{"name":"Department of Microbiology, College of Medicine, Korea University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji 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College of Medicine, Korea University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man-Seong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology, College of Medicine, Korea University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dokeun","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency","place":["Cheongju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You-Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency","place":["Cheongju, Republic of 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