{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:23:14Z","timestamp":1785864194314,"version":"3.56.0"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015793","name":"Honghui Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015793","id-type":"DOI","asserted-by":"publisher"}]}],"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>Human cytomegalovirus (HCMV) induces severe morbidity and mortality in neonates, organ transplant recipients, and immunocompromised individuals. Currently, there is no licensed vaccine for HCMV. Given its ability to elicit a robust and enduring CD8 T cell response, we designed a recombinant adenovirus vaccine, referred to as the rAdMev vaccine, using bioinformatics methods based on human cytomegalovirus multi-antigen epitopes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Five proteins of HCMV (pp150, pp65, gB, gH, IE1) were analyzed using bioinformatics tools, and 58 T cell epitopes, 66 Th cell epitopes, and 15 B cell epitopes were screened out. The immunogenicity of the overlapping candidate peptides was initially tested\n                      <jats:italic>in vitro<\/jats:italic>\n                      using molecular docking techniques and flow cytometry. Subsequently, the selected dominant antigenic epitopes were recombined into the adenovirus vector. To enhance the vaccine\u2019s efficacy, we employed a mixed priming schedule, combining an adenoviral vaccine with a protein vaccine. Finally, the immune response induced by heterologous vaccination was analyzed by proteomics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The developed vaccine demonstrates favorable characteristics in terms of major histocompatibility complex affinity, immunogenicity, and population coverage. Primary immunization of mice with the rAdMev vaccine induces a potent innate immune response, characterized by highly activated dendritic cell subsets and the polarization of macrophages towards the M1 phenotype. Heterologous vaccination fosters the generation of robust polyfunctional (IFN-\u03b3, TNF, IL-2, Granzyme B, Perforin) CD8 T cell responses, leading to the establishment of persistent effector memory T cells. Furthermore, we observed that heterologous vaccination activates fatty acid \u03b2-oxidation through the PPAR signaling pathway, enhancing mitochondrial biogenesis and promoting CD8 T cell memory formation\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We have developed a novel multi-epitope recombinant adenovirus vaccine that can elicit long-lasting antiviral cellular immunity, providing new insights into the development of vaccines against HCMV.<\/jats:p>\n                  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