{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:33:57Z","timestamp":1789515237103,"version":"build-2803163510"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"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>\n                      SARS-CoV-2 is continuing to prevail as an endemic virus, and therefore, we need a next-generation vaccine that prevents SARS-CoV-2 infections, broadly protects against multiple CoVs, and induces long-term local and systemic immunity. To address that need, we have designed a mixed lipopeptide-based pan-coronavirus (LP\n                      <jats:sub>Mix<\/jats:sub>\n                      ) vaccine based on T and B cell epitopes derived from highly conserved and functional regions of the SARS-CoV-2 spike (S), nucleocapsid (N), and membrane (M) proteins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male C57BL\/6 mice (n=5 per group) were immunized intranasally twice, 14 days apart, with the LP\n                      <jats:sub>Mix<\/jats:sub>\n                      vaccine candidates, which consisted of seven lipopeptides (LP1\u2013LP7), with or without HKCC (heat-killed\n                      <jats:italic>Caulobacter crescentus<\/jats:italic>\n                      ), a novel mucosal adjuvant. At 2.5 weeks, 2 months, and 7 months post-immunization, lung, spleen, bone marrow, and bronchoalveolar lavage (BAL) samples were collected for immunological analyses. Additionally, blood samples were collected monthly to monitor antibody titers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We demonstrate that intranasal immunizations of mice with LP\n                      <jats:sub>Mix<\/jats:sub>\n                      induced a long-lasting systemic IgM\/IgG, and mucosal IgA response against a broad-spectrum of CoVs, showing clinically significant levels of neutralizing antibody titers. Splenocytes and bone marrow cells, derived from LP\n                      <jats:sub>Mix<\/jats:sub>\n                      immunized mice, demonstrated a robust proliferation response against vaccine antigens (P\n                      <jats:sub>1-7<\/jats:sub>\n                      ), which were maintained up to 2 months and 7 months, after LP\n                      <jats:sub>Mix<\/jats:sub>\n                      immunizations, respectively. Moreover, antigen-specific B cells and memory CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were long-lived and maintained up to 7 months after LP\n                      <jats:sub>Mix<\/jats:sub>\n                      immunizations, in the lungs, spleen and bone marrow. The addition of HKCC (heat-killed\n                      <jats:italic>Caulobacter crescentus<\/jats:italic>\n                      ), a novel mucosal adjuvant, promoted the longevity of memory CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell and B cell responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Overall, our study demonstrates that a mucosal lipopeptide-based vaccine targeting conserved SARS-CoV-2 epitopes elicits durable, long-lasting immune responses against a broad range of coronaviruses.<\/jats:p>\n                  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