{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:55:17Z","timestamp":1784224517730,"version":"3.55.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"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>Objective<\/jats:title>\n                    <jats:p>To evaluate the synergistic immunological protection of exosomal T-cell epitope vaccine and antibody-inducing vaccine against SARS-CoV-2 in highly humanized mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Red blood cell-derived exosomes were loaded with 27 CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell epitope peptides and 19 CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell epitope peptides followed by combined immunization with S1 protein vaccine of SARS-CoV-2 and adjuvant poly I:C in HLA-A2\/DR1 double transgenic mice. After immunizations, splenocytes were assessed for epitope-specific T cell responses by intracellular cytokine staining and ELISPOT, and for functional T cell subset analysis through flow cytometry. Meanwhile, serum anti-S1 protein IgG and neutralizing antibodies were quantified via ELISA and BA.5 pseudovirus neutralization assay, respectively. Furthermore, viral challenge was performed after the combined immunization in HLA-A2\/DR1\/hACE2 triple transgenic mice, followed by viral load quantification, viral protein detection, and H&amp;amp;E staining in lungs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The combined immunization i) increased the titers of S1 protein-specific IgG antibodies and neutralizing antibodies as well as Tfh cell frequency as compared to the S1 protein vaccine alone; ii) induced significantly more S1 protein-specific T cells and effector memory CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells, and inhibited T cell exhaustion and regulatory T cell differentiation, compared to the exosomal T-cell epitope vaccine alone; iii) achieved the lowest pulmonary viral loads, inflammatory cell infiltration, and histopathological damage after SARS-CoV-2 infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study, for the first time, demonstrates the synergistic humoral and cellular immune responses and protective efficacy induced by the combined immunization of exosomal T-cell epitope vaccine and antibody-inducing vaccine, and provides preclinical evidence from highly humanized mice for optimizing next-generation SARS-CoV-2 vaccine protocols.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1729444","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T06:30:51Z","timestamp":1770100251000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic immune protection of exosomal T-cell epitope vaccine and antibody-inducing vaccine 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