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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\n                  <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                  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.\n                <\/jats:p>","DOI":"10.64898\/2026.09.11.751026","type":"posted-content","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:40:15Z","timestamp":1789742415000},"source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporal control of STING activation and saRNA delivery decouples humoral and cellular immunity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2441-6409","authenticated-orcid":false,"given":"David J.","family":"Peeler","sequence":"first","affiliation":[{"name":"Department of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College London, SW7 2AZ, UK"},{"name":"Department of Infectious Disease, Imperial College London, SW7 2AZ, UK"},{"name":"Department of Physiology, Anatomy and 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