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Using a mouse model of human metapneumovirus (HMPV), we found viral burden was higher in nasal airways and exhibited delayed clearance. Despite high burden, there was low nasal expression of type I and III interferon (IFN). Single-cell RNA-sequencing (scRNA-Seq) from HMPV-infected mice showed lower nasal IFN-stimulated gene (ISG) expression and nasal enrichment of genes negatively regulating IFN. scRNA-Seq of patients with COVID-19 verified lower ISG expression in upper airways. HMPV infection downregulated nasal expression of IFN regulatory factor 3, suggesting a mechanism for limited response. To rescue the quiescent environment, we administered type I or III IFN to upper airways early postinfection, leading to lower nasal HMPV titer and virus-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell upregulation. Intranasal immunization adjuvanted with type I or III IFN improved immune response, reduced clinical disease, and enhanced viral clearance in HMPV and influenza infection. IFN adjuvant increased recruitment of dendritic cells, recruitment of resident memory T cells, and neutralizing antibodies. These findings reveal locally suppressed IFN production contributes to a quiescent nasal immune landscape that delays viral clearance and impairs mucosal vaccine responses.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.182836","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T16:00:38Z","timestamp":1758038438000},"source":"Crossref","is-referenced-by-count":5,"title":["Limited nasal IFN production contributes to delayed respiratory virus clearance and suboptimal vaccine responses"],"prefix":"10.1172","volume":"10","author":[{"given":"Jorna","family":"Sojati","sequence":"first","affiliation":[{"name":"Department of Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia B.","family":"Parks","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Eddens","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John V.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"},{"name":"Department of Microbiology & Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA."},{"name":"Institute for Infection, Immunity, and Inflammation in Children, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"University of Wisconsin\u2013Madison School of Medicine and Public Health, Madison, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"B1","unstructured":"WHO. 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