{
  "abstract": "Self-amplifying mRNA (saRNA) vaccine formulations link the location and timing of antigen expression to innate immune stimulation by both RNA cargo and carrier. We hypothesized that targeting a polymeric STING agonist prodrug (polySTING) to antigen-presenting cells (APCs) independently of saRNA delivery could tune vaccines responses without limiting saRNA expression. By varying the time and location of STING signaling relative to saRNA delivered by muscle-restricted (polyplex, PP) and lymph node-draining (lipid nanoparticle, LNP) saRNA formulations, we studied how spatiotemporal colocalization of type I interferon (IFN-I) and antigen expression impacts innate and adaptive vaccine responses. Co-administering PP + polySTING decreased antigen-specific adaptive type 1 responses by mismatching early lymph node IFN-I and later arriving antigen; this could be reversed by delaying polySTING delivery timing. Conversely, synchronizing early LNP saRNA delivery and polySTING IFN-I in the lymph node boosted saRNA type 1 T cell responses without impacting humoral immunity, which re-directed antigen-intrinsic immune skewing and enhanced protection against pulmonary Acinetobacter baumannii challenge. Collectively, these findings define formulation-specific innate immune responses to saRNA vaccines and establish APC-targeted adjuvants as a strategy to tune saRNA vaccine immunogenicity.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College London, UK; Department of Infectious Disease, I"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "D. J. Peeler"
    },
    {
      "name": "Z. Wang"
    },
    {
      "name": "L. Spiga"
    },
    {
      "name": "S. Jokonya"
    },
    {
      "name": "C. Thomas"
    },
    {
      "name": "D. Reumann"
    },
    {
      "name": "K. Shramko"
    },
    {
      "name": "L. Rigat Nogareda"
    },
    {
      "name": "P. F. McKay"
    },
    {
      "name": "D. C. Nguyen"
    },
    {
      "name": "M. Briones Orta"
    },
    {
      "name": "P. S. Stayton"
    },
    {
      "name": "M. M. Stevens"
    },
    {
      "name": "R. J. Shattock"
    },
    {
      "name": "J. S. Tregoning"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f6khdvs7kpabq.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.11.751026",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.751026v1.full",
  "id": "f6khdvs7kpabq",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.751026v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|Immunotherapy and Immune Responses"
    ]
  ],
  "openalex": "W7213556253",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.751026v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f6khdvs7kpabq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:02Z",
      "native_id": "10.64898/2026.09.11.751026",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.11.751026v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Spatiotemporal control of STING activation and saRNA delivery decouples humoral and cellular immunity",
  "title_text": "Spatiotemporal control of STING activation and saRNA delivery decouples humoral and cellular immunity",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:02Z",
  "url": "https://research.draconitic.com/paper/f6khdvs7kpabq",
  "venue": "bioRxiv",
  "versions": []
}