{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE347nnn/GSE347532/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE347532"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Intranasal live vaccine harnesses pre-existing T cell memory for broad influenza protection","description":"Influenza A virus (IAV) continually drives seasonal epidemics and pandemics through antigenic evolution, yet conventional vaccines afford limited cross-protection due to their subtype-restricted antibody responses. Respiratory tissue-resident memory T (TRM) cells recognize conserved epitopes and serve as key effectors against heterosubtypic IAV, but effective induction strategies remain elusive. Here we show that the CA4-dNS1 live attenuated influenza nasal spray vaccine confers broad heterosubtypic protection against circulating IAVs via pulmonary TRM induction, independent of cross-reactive antibodies. Notably, pre-existing memory T cells, established by prior infection or intramuscular vaccination, are efficiently recruited by nasal boosting and differentiate into functional pulmonary TRM, substantially augmenting protective efficacy. Mechanistically, intramuscular priming expands the central memory T (TCM) pool, whereas nasal spray vaccination acts as a \"portal-of-entry\" immunization that both induces local TRM maturation and directs circulating TCM trafficking to the respiratory mucosa, thereby establishing a robust local immune barrier. This paradigm is generalizable to other vector-based nasal spray vaccines, providing a strategic framework for universal influenza vaccine development and for harnessing pre-existing immunity in mucosal vaccine design.","dates":{"publication":"2026/09/21"},"accession":"GSE347532","cross_references":{"GSM":["GSM10054794","GSM10054793","GSM10054792","GSM10054791","GSM10054787","GSM10054798","GSM10054797","GSM10054796","GSM10054795","GSM10054789","GSM10054788","GSM10054790"],"GPL":["24247"],"GSE":["347532"],"taxon":["Mus musculus"]}}