{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T18:08:40Z","timestamp":1790446120801,"version":"4.1.0"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"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><jats:title>Introduction<\/jats:title><jats:p>Vaccines against intracellular pathogens like <jats:italic>Mycobacterium tuberculosis (M. tuberculosis)<\/jats:italic> require the induction of effective cell-mediated immunity. Adjuvants primarily enhance antigen-induced adaptive immunity by promoting the activation of antigen-presenting cells (APCs).This study is to develop an adjuvant targeted to dendritic cells (DCs), one of the main APCs, so as to assist in inducing a long-term cellular immune response to <jats:italic>M. tuberculosis<\/jats:italic> protein antigens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Polylactic-co-glycolic acid-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) modified with Triantennary N-Acetylgalactosamine (Tri-GalNAc) were prepared to target DCs. Additionally, the stimulator of interferon genes (STING) agonist SR717 was encapsulated within PLGA-PEG NPs to activate DCs. Meanwhile, <jats:italic>M. tuberculosis<\/jats:italic> fusion protein (TP) was encapsulated in PLGA-PEG NPs to construct vaccine candidates: TP\/Tri-GalNAc-PLGA-PEG-SR717 (TP\/GPS in short) and TP\/ Tri-GalNAc-PLGA-PEG (TP\/GP in short). The targeting and activation effects of these NPs were assessed <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, and their immunogenicity were evaluated in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Tri-GalNAc modification significantly enhanced the targeting of NPs to DCs, and encapsulated SR717 effectively promoted the maturation and activation of DCs. TP\/GPS elicited a potent antigen-specific T cell immune response and successfully induced long-term immune memory in mice. Moreover, after the mice were infected with H37Ra <jats:italic>via<\/jats:italic> nasal instillation, TP\/GPS significantly reduced the bacterial load in their lungs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Tri-GalNAc-modified PLGA-PEG NPs in combination with SR717 targeted and activated DCs, effectively assisting <jats:italic>M. tuberculosis<\/jats:italic> antigen in inducing long-term T cell-mediated immunity. This approach offers an innovative and effective adjuvant strategy for the development of subunit vaccine against intracellular pathogen.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1490003","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T06:40:23Z","timestamp":1734936023000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Enhancing cell-mediated immunity through dendritic cell activation: the role of Tri-GalNAc-modified PLGA-PEG nanoparticles encapsulating 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