Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intranasal live vaccine harnesses pre-existing T cell memory for broad influenza protection

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE347532 | GEO | 2026/09/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE347532_RAW.tar	Raw
	filelist.txt	Txt

Items per page:

1 - 3 of 3

Similar Datasets

Nasal CD4⁺ tissue-resident memory T cells provide cross-protective immunity to influenza

Project description:CD4 tissue-resident memory T cells (TRM) are crucial adaptive immune components involved in preventing influenza A virus (IAV) infection. Despite their importance, their physiological role in the upper respiratory tract, the first site of contact with IAV, remains unclear. Here, we find that, after IAV infection, antigen-specific CD4 TRM persist in the nasal tissue (NT) compartment after infection and provide protection upon heterosubtypic challenge. Single cell RNA sequencing analysis reveals that NT CD4 TRM are heterogeneous and transcriptionally distinct as compared to their lung counterparts. Mechanistically, we demonstrate that the CXCR6-CXCL16 axis promotes CD4 TRM residency in the NT. Furthermore, we show that the NT of mice and humans contains a high frequency of Th17 CD4 TRM that aid in local viral clearance and in reducing tissue damage. Collectively, our results support a robust physiological role for nasal tissue CD4 TRM in local protection during heterosubtypic IAV infection.

2026-02-26 | GSE270932 | GEO

Dynamic equilibrium of lung Trm dictates waning immunity after IAV infection

Project description:Lung resident memory (Trm) CD8 T cells induced by influenza A virus (IAV), are pivotal for providing heterosubtypic immunity, but are not maintained long term, causing gradual loss of protection. This contrasts sharply with long-term maintenance of Trm induced by localized infections of the skin and other tissues. Here we show that the decline in lung Trm is determined by an imbalance between apoptosis and lung recruitment/conversion to Trm of circulating memory cells. At the cellular level, circulating effector memory (Tem) rather than central memory (Tcm) cells are the precursors for conversion to lung Trm. Time-dependent changes in expression of genes critical for Trm differentiation together with enrichment of Tcm diminish the capacity of circulating memory CD8 T cells to form Trm, explaining why IAV-induced Trm are not stably maintained over time. Importantly, systemic booster immunization, through increasing the number of circulating Tem cells, induces an increase in lung Trm pool, providing a new rational for future IAV vaccines.

2016-11-18 | GSE86973 | GEO

Dynamic landscapes and protective immunity coordinated by influenza-specific lung-resident memory CD8+ T cells revealed by intravital imaging

Project description:Lung tissue-resident memory CD8+ T-cells (Trm) are critical for heterosubtypic immunity against influenza virus-(IAV)-reinfection. How these cells surveil the lung, respond to infection and interact with other cells remains unresolved. Here, we used mouse models to identify and enrich lung Trm in combination with intravital and static imaging to assess spatiotemporal dynamics of IAV-induced lung TRM before and after recall-infection. CD69+CD103+ Trm localize to sites of prior influenza infection where they exhibit substantially slower movement properties than non-Trm that also surveil the lung. After rechallenge, lung Trm form tight clusters in an antigen-dependent manner. IAV-specific Trm express several factors that regulate myeloid cell biology and their protective immune responses are accompanied by activation and migration of dendritic cells to draining lymph nodes and recruitment of inflammatory monocytes. Overall, these data reveal the dynamic landscapes of lung Trm cells associated with early protective immunity against IAV infection.

2024-07-22 | GSE242558 | GEO

Atomistic TCR-ligand interactions instruct memory T-cell differentiation and crossreactivity

Project description:While memory T-cells provide protective immunity against specific pathogens, their post-encounter differentiation into central (TCM) and/or effector (TEM) subpopulations remains enigmatic. We thus explored the CD8 T-cell receptor (TCR) repertoire of 242 murine TCR clonotypes directed against an immunodominant influenza A virus (IAV) peptide/major histocompatibility complex (pMHC) ligand, the nucleoprotein NP366-374/Db, leveraging single-cell transcriptomics with paired TCR sequencing, mechanosensing metrics, and in vivo memory development plus TCR-pMHC structural analyses. Polar TEM and more variegated TCM repertoires as well as bipotential “bipolar” clonotypes (TBP) revealed weak force-dependent bonding parameters associated with heterosubtypic IAV crossreactivities. TCM and TEM polarities manifest pMHC binding skewed to TCR- versus TCR-subunit mechanotransduction, respectively, unlike the more signaling-balanced TBP TCRs. In sum, TCR diversity anticipates pathogen evolution whereas divergent signaling regulates memory fate.

2026-02-18 | GSE302680 | GEO

Atomistic TCR-ligand interactions instruct memory T-cell differentiation and crossreactivity

Project description:While memory T-cells provide protective immunity against specific pathogens, their post-encounter differentiation into central (TCM) and/or effector (TEM) subpopulations remains enigmatic. We thus explored the CD8 T-cell receptor (TCR) repertoire of 242 murine TCRαβ clonotypes directed against an immunodominant influenza A virus (IAV) peptide/major histocompatibility complex (pMHC) ligand, the nucleoprotein NP366-374/Db, leveraging single-cell transcriptomics with paired TCR sequencing, mechanosensing metrics, and in vivo memory development plus TCR-pMHC structural analyses. Polar TEM and more variegated TCM repertoires as well as bipotential “bipolar” clonotypes (TBP) revealed weak force-dependent bonding parameters associated with heterosubtypic IAV crossreactivities. TCM and TEM polarities manifest pMHC binding skewed to TCRβ- versus TCRα-subunit mechanotransduction, respectively, unlike the more signaling-balanced TBP TCRs. In sum, TCR diversity anticipates pathogen evolution whereas divergent signaling regulates memory fate.

2026-02-18 | GSE302856 | GEO

Atomistic TCR-ligand interactions instruct memory T-cell differentiation and crossreactivity [RNA-seq]

Project description:While memory T-cells provide protective immunity against specific pathogens, their post-encounter differentiation into central (TCM) and/or effector (TEM) subpopulations remains enigmatic. We thus explored the CD8 T-cell receptor (TCR) repertoire of 242 murine TCRαβ clonotypes directed against an immunodominant influenza A virus (IAV) peptide/major histocompatibility complex (pMHC) ligand, the nucleoprotein NP366-374/Db, leveraging single-cell transcriptomics with paired TCR sequencing, mechanosensing metrics, and in vivo memory development plus TCR-pMHC structural analyses. Polar TEM and more variegated TCM repertoires as well as bipotential “bipolar” clonotypes (TBP) revealed weak force-dependent bonding parameters associated with heterosubtypic IAV crossreactivities. TCM and TEM polarities manifest pMHC binding skewed to TCRβ- versus TCRα-subunit mechanotransduction, respectively, unlike the more signaling-balanced TBP TCRs. In sum, TCR diversity anticipates pathogen evolution whereas divergent signaling regulates memory fate.

2026-08-05 | GSE313272 | GEO

An inactivated multivalent influenza A virus vaccine is broadly protective in mice and ferrets [ferret]

Project description:Influenza A viruses (IAVs) present major public health threats from annual seasonal epidemics and pandemics as well as from viruses adapted to a variety of animals including poultry, pigs, and horses. Vaccines that broadly protect against all such IAVs, so-called “universal” influenza vaccines, do not currently exist, but are urgently needed. Here, we demonstrated that an inactivated, multivalent whole virus vaccine, delivered intramuscularly or intranasally, was broadly protective against challenges with multiple IAV hemagglutinin and neuraminidase subtypes in both mice and ferrets. The vaccine is comprised of four beta-propiolactone-inactivated low pathogenicity avian influenza A virus subtypes of H1N9, H3N8, H5N1, or H7N3. Vaccinated mice and ferrets demonstrated substantial protection against a variety of IAVs, including the 1918 H1N1 strain, the highly pathogenic avian H5N8 strain, and H7N9. We also observed protection against challenge with antigenically variable and heterosubtypic avian, swine, and human viruses. Compared to mock vaccinated animals, vaccinated mice and ferrets demonstrated marked reductions in viral titers, lung pathology, and host inflammatory responses. This vaccine approach indicates the feasibility of eliciting broad, heterosubtypic IAV protection and identifies a promising candidate for influenza vaccine clinical development.

2022-07-21 | GSE205840 | GEO

An inactivated multivalent influenza A virus vaccine is broadly protective in mice and ferrets [mouse]

2022-07-21 | GSE205839 | GEO

Single cell CITE-seq and VDJ sequencing of CD8+ central memory blood T cells (TCM) and their in-vivo matured tissue-resident memory-like T cells (TRM)

Project description:The aim of the experiment was to understand the clonal relationship between CD8+ central memory blood T cells (TCM) and the in-vivo matured TCM tissue-resident memory-like T cells (TRM) on day 14. TCM were FACS sorted from human PBMCs (n=5). Half of the cells were processed on day 1 and half of the cells of each donor were matured into TRM with anti-CD3, IL-15 and TGF beta for 14 days. Both day 1 TCM and matured day 14 TRM-like cells were further processed using the 5´10X genomics workflow.

2023-06-12 | E-MTAB-12840 | biostudies-arrayexpress

Primary nasal viral infection rewires the tissue-scale memory response

Project description:The nasal mucosa is frequently the initial site of respiratory viral infection, replication, and transmission, but the cellular composition at homeostasis, during infection, and during a memory response are poorly understood. Here, we generated a single-cell RNA-sequencing (scRNA-seq) atlas of the murine nasal mucosa sampling three distinct regions before and during primary and secondary influenza A virus (IAV) infection. Primary infection was largely restricted to respiratory mucosa and induced stepwise changes in immune and epithelial cell type, subset, and state composition over time. Following viral clearance (14 dpi), rare, previously undescribed Krt13+ nasal immune-interacting floor epithelial (KNIIFE) cells expressing multiple genes with immune communication potential increased concurrently with tissue-resident memory T (TRM)-like cells and early IgG+/IgA+ plasmablasts. Proportionality analysis coupled with cell-cell communication inference, alongside validation by in situ microscopy, underscored the CXCL16–CXCR6 signaling axis between MDMs and effector CD8 T cells 8dpi and KNIIFE cells and TRM cells 14 dpi. Secondary influenza challenge with a homologous or heterologous strain administered 60 dpi induced an accelerated and coordinated myeloid and lymphoid response without epithelial proliferation, illustrating how tissue-scale memory to natural infection engages both myeloid and lymphoid cells to reduce epithelial regenerative burden. Raw and processed single-cell counts matrices can be accessed and downloaded from the Broad Institute Single-Cell Portal from studies SCP2216 and SCP 2221.

2024-06-17 | GSE266469 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data