{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:21:14Z","timestamp":1790000474669,"version":"4.0.1"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"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                      Adhesion to host cells is the first and essential step in\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      (\n                      <jats:italic>M. tuberculosis<\/jats:italic>\n                      ) infection. Among adhesion molecules, the PGRS domain of PE_PGRS33 plays a critical role in invasion but is dominated by B cell epitopes and lacks sufficient T cell epitopes, restricting its capacity to induce a balanced immune response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To overcome this limitation, we employed an integrative reverse vaccinology pipeline combining computational prediction and experimental validation. Helper and cytotoxic T lymphocyte epitopes were incorporated from multiple\n                      <jats:italic>M. tuberculosis<\/jats:italic>\n                      adhesins as well as other virulence-associated proteins, and adjuvant sequences were systematically evaluated in silico.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among three multi-epitope constructs, the Toll-like receptor 2 (TLR2)-agonist and  pan HLA DR-binding epitope (PADRE)-adjuvanted vaccine (TLR2-vaccine) emerged as the most promising candidate. In murine models, TLR2-vaccine induced strong antigen-specific antibody and IFN-\u03b3 responses, significantly reduced bacterial loads following H37Ra challenge, and effectively prevented extrapulmonary dissemination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings highlight the potential of adhesin-inclusive multi-epitope vaccines to elicit both humoral and cellular immunity and demonstrate how computational vaccinology can accelerate the development of targeted interventions against tuberculosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1707471","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T06:37:01Z","timestamp":1763534221000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["A multi-epitope vaccine incorporating adhesin-derived antigens protects against Mycobacterium tuberculosis infection and 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