{
  "abstract": "mRNA vaccines can encode multiple tumor antigens whose presentation ultimately depends on adequate intracellular processing. To evaluate the potential impact of epitope-flanking sequences, we compared the immunogenicity of two mRNA vaccines in the MC38 mouse model. Both vaccines coded for the same tumor-specific antigens (TSAs). The only difference between the two vaccines was the identity of the epitope-flanking amino acids. The vaccine encoding TSAs bordered by optimized flanking sequences (TSA-Opti) cleared established tumors and elicited robust CD8⁺ T-cell responses. In contrast, the vaccine encoding the same TSAs surrounded by natural flanking sequences (TSA-Nat) induced weaker responses and incomplete protection against tumor growth. Quantitative immunopeptidomics showed that TSA-Opti increased antigen presentation levels, providing a mechanistic link between flanking-sequence design and the enhanced magnitude, clonal diversity, and functionality of TSA-specific CD8+ T cells. TSA-Opti further promoted durable memory, conferring long-term protection against tumor rechallenge. These results identify epitope-flanking sequences as tunable design elements that control peptide-MHC I density and thereby shape the magnitude, clonal diversity, tissue localization, and durability of antitumor CD8⁺ T-cell immunity.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada.",
    "Epitopea, Inc., Montréal, QC H3T 1J4, Canada.",
    "Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada.",
    "Cognate Biotechnology Research, Montréal, QC H2S 3H1, Canada.",
    "Department of Chemistry, Université de Montréal, Montréal, QC H2V 0B3, Canada.",
    "Department of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Marie-Pierre Hardy",
      "orcid": "0000-0003-1316-6483"
    },
    {
      "affs": [
        0
      ],
      "name": "Gabriel Ouellet-Lavallée"
    },
    {
      "affs": [
        0
      ],
      "name": "Catherine Thériault"
    },
    {
      "affs": [
        0
      ],
      "name": "Chantal Durette",
      "orcid": "0000-0002-6692-1262"
    },
    {
      "affs": [
        1
      ],
      "name": "Krystel Vincent"
    },
    {
      "affs": [
        0
      ],
      "name": "Robin Minati",
      "orcid": "0000-0002-8663-6645"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabelle Caron"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Assya Trofimov",
      "orcid": "0000-0001-8748-3735"
    },
    {
      "affs": [
        0
      ],
      "name": "Joel Lanoix",
      "orcid": "0000-0001-7073-9298"
    },
    {
      "affs": [
        0
      ],
      "name": "Jean-Philippe Laverdure",
      "orcid": "0000-0002-9245-6413"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Pierre Thibault",
      "orcid": "0000-0001-5993-0331"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Claude Perreault",
      "orcid": "0000-0001-9453-7383"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dtr68ev9w05wq.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15191753",
  "fulltext_url": "https://europepmc.org/articles/PMC13664092",
  "id": "dtr68ev9w05wq",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://europepmc.org/article/MED/42882451",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Immunotherapy and Immune Responses"
    ]
  ],
  "openalex": "W7214637814",
  "pdf_url": "https://europepmc.org/articles/PMC13664092?pdf=render",
  "pmcid": "PMC13664092",
  "pmid": "42882451",
  "published": "2026-09-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dtr68ev9w05wq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42882451",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42882451"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunotherapy and Immune Responses",
      "subfield": "immunology"
    }
  ],
  "title": "Optimized Epitope-Flanking Sequences Enhance Antigen Presentation and T-Cell Responses Following mRNA Vaccination.",
  "title_text": "Optimized Epitope-Flanking Sequences Enhance Antigen Presentation and T-Cell Responses Following mRNA Vaccination.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/dtr68ev9w05wq",
  "venue": "Cells",
  "versions": []
}