{
  "abstract": "Tuberculosis (TB) remains the leading cause of death from a single infectious agent worldwide, highlighting the need for improved vaccines beyond the limited protection currently provided by the Bacillus Calmette-Guérin (BCG) vaccine. Here we investigated the immunological impact of incorporating alpha-Galactosylceramide (αGC) into mRNA lipid nanoparticles (mRNA-LNPs) as a vaccination strategy against Mycobacterium tuberculosis (Mtb), the pathogen causing TB. Using Mtb antigens ESAT-6 and Ag85B, we demonstrate that αGC-adjuvanted mRNA-LNPs induce controlled activation of invariant natural killer T (iNKT) cells, thereby reshaping vaccine-induced immunity. Specifically, αGC incorporation promoted the generation of CD44 ⁺ CD69 ⁺ CD62L ⁻ CD4 ⁺ T cells in the spleen and altered the CD4 ⁺ T -helper (T H ) profile through the addition of modest T H 2 and T H 17 responses alongside robust T H 1 immunity. Furthermore, antigen-specific CD8 ⁺ T-cell responses against ESAT-6 and Ag85B were observed exclusively in the genetically diverse CB6F1/J mouse model, highlighting the importance of host genetic background in evaluating mRNA vaccine immunogenicity after homologous vaccination strategies. Finally, we demonstrate that using a heterologous prime–pull strategy combining intramuscular mRNA vaccination with local antigen instillation increased the frequency of antigen-specific lung-associated CD4 ⁺ T cells displaying a tissue residency-associated phenotype, with additional contribution of αGC adjuvantation to this response. In summary, these findings provide novel insights into αGC adjuvant-mediated immune modulation of mRNA vaccines and support further testing of protective efficacy of this approach against TB.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Physical Pharmacy and General Biochemistry, Department of Pharmaceutics, Ghent Research Group on Nanomedicines, Ghent University",
    "Immunobiology and Therapy Unit, Inserm U1224, Institut Pasteur, Université Paris Cité",
    "Laboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University",
    "Department of Biomolecular Medicine, Ghent University",
    "Vlaams Instituut voor Biotechnologie (VIB) Center for Medical Biotechnology, VIB",
    "Translational Oncology Research Centre, Department of Biomedical Sciences, Vrije Universiteit Brussel (VUB)"
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ilke Aernout"
    },
    {
      "affs": [
        0
      ],
      "name": "Thomas Ehouarne"
    },
    {
      "affs": [
        0
      ],
      "name": "Kevin Mwangi"
    },
    {
      "affs": [
        1
      ],
      "name": "Kia C. Ferrell"
    },
    {
      "affs": [
        0
      ],
      "name": "Margo De Velder"
    },
    {
      "affs": [
        0
      ],
      "name": "Janne Swinnen"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Aaron Verplancke"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Laura Van Moortel"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Margaux De Meyer"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Patrick Willems"
    },
    {
      "affs": [
        5
      ],
      "name": "Lorenzo Franceschini"
    },
    {
      "affs": [
        5
      ],
      "name": "Karine Breckpot"
    },
    {
      "affs": [
        0
      ],
      "name": "Stefaan C. De Smedt"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Francis Impens"
    },
    {
      "affs": [
        1
      ],
      "name": "Caroline Demangel"
    },
    {
      "affs": [
        0
      ],
      "name": "Rein Verbeke"
    },
    {
      "affs": [
        0
      ],
      "name": "Ine Lentacker"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/58nbejdfnjp9z.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1929726",
  "fulltext_url": "https://europepmc.org/articles/PMC13677840",
  "id": "58nbejdfnjp9z",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1929726/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7214249765",
  "pdf_url": "https://europepmc.org/articles/PMC13677840?pdf=render",
  "pmcid": "PMC13677840",
  "pmid": "42898436",
  "published": "2026-10-05",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/58nbejdfnjp9z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1929726",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1929726/full"
    },
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42898436",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42898436"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|Tuberculosis Research and Epidemiology",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Alpha-galactosylceramide as mRNA vaccine adjuvant modulates cellular immunity against tuberculosis and contributes to antigen-specific lung-associated T cells with a TRM-associated phenotype following prime-pull strategy",
  "title_text": "Alpha-galactosylceramide as mRNA vaccine adjuvant modulates cellular immunity against tuberculosis and contributes to antigen-specific lung-associated T cells with a TRM-associated phenotype following prime-pull strategy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/58nbejdfnjp9z",
  "venue": "Frontiers in Immunology",
  "versions": []
}