{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:40:17Z","timestamp":1790912417774,"version":"4.1.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The emergence of immune-evasive SARS-CoV-2 variants has exposed limitations in the breadth and durability of protection conferred by current Spike-based vaccines, highlighting the need for next-generation approaches targeting conserved viral regions. Here, we describe the design and preclinical evaluation of an optimized multi-epitope vaccine, CoV2-BMEPu.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CoV2-BMEPu was rationally designed using immunological data from SARS-CoV-2 convalescent cohorts, incorporating conserved and immunodominant regions from the Spike (S), Membrane (M) and Nucleocapsid (N) proteins, together with selected receptor-binding domain (RBD) segments associated with broadly neutralizing antibodies. The construct was engineered as a secreted trimeric antigen and delivered as an mRNA vaccine formulated in lipid nanoparticles (LNPs).\n                      <jats:italic>In vitro<\/jats:italic>\n                      expression, innate immune activation, immunogenicity and protective efficacy were evaluated in cell systems and mouse models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>mRNA-BMEPu was efficiently expressed in vitro as soluble oligomers and triggered innate immune activation in human macrophages. In C57BL\/6 mice, LNP-BMEPu elicited robust binding and neutralizing antibodies against the ancestral virus and antigenically distant Omicron subvariants. Vaccination also induced strong and polyfunctional CD8\u207a T cell and T follicular helper responses that persisted over time. In K18-hACE2 transgenic mice, immunization conferred complete protection against lethal SARS-CoV-2 challenge, with effective control of viral replication and reduced lung inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These results support CoV2-BMEPu as a next-generation multi-epitope mRNA vaccine candidate capable of inducing broad, durable and protective immunity against current and emerging SARS-CoV-2 variants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1787877","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:32:26Z","timestamp":1777959146000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Preclinical evaluation of a multi-epitope mRNA vaccine platform for broad and durable SARS-CoV-2 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Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Flores","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Centro Nacional de Biotecnolog\u00eda (CNB), Consejo Superior de Investigaciones Cient\u00edficas (CSIC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Casasnovas","sequence":"additional","affiliation":[{"name":"Department of Microbial Biotechnology, CNB, CSIC","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tirso","family":"Pons","sequence":"additional","affiliation":[{"name":"Department of Immunology and Oncology, CNB, CSIC","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Oscar S.","family":"Sorzano","sequence":"additional","affiliation":[{"name":"Biocomputing Unit and Computational Genomics, CNB, CSIC","place":["Madrid, 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