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MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines

ABSTRACT: MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines

PROVIDER: PRJNA1301826 | ENA |

REPOSITORIES: ENA

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MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines [MAIT]

Project description:Adenoviral (Ad) vectors and mRNA vaccines exhibit distinct patterns of immune responses, with reactogenicity influencing their use during and beyond the COVID-19 pandemic. However, despite the clinical significance, the underpinning mechanisms remain unclear. Innate and innate-like lymphocytes, such as mucosal-associated invariant T cells, are highly sensitive to cytokines and can enhance both innate and adaptive vaccine responses. We compared longitudinal human immune responses and reactogenicity following homologous ChAdOx1 nCoV-19 and BNT162b2 vaccination to define the interactions between innate-like lymphocytes and adaptive immunity – and their in vivo consequences. Specifically, Ad vector priming elicited robust early type I interferon (IFN)-mediated activation of innate-like T cells, augmenting T cell responses (innate to adaptive signalling), which diminished upon boosting in the presence of anti-vector immunity. In contrast, mRNA vaccine responses in innate-like cells were markedly enhanced after boosting. This was initiated by IFN-γ signalling from spike-specific memory T cells and amplified by IFN-γR+ innate-like lymphocyte networks (adaptive to innate signalling). Importantly, extending the interval between doses reduced inflammatory responses to mRNA vaccination. In an independent clinical trial, spike-specific T cells predicted severe reactogenicity to mRNA vaccine boosting regardless of the dosing interval and vaccine type. These findings reveal a close integration of innate-like and adaptive responses to novel vaccines, including an IFN-γ-mediated function of innate-like T cells in orchestrating critical early responses to mRNA vaccines which may have significant implications for optimising future vaccine regimens.

2025-08-29 | GSE304584 | GEO

MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines [MAIT]

Project description:MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines [MAIT]

| PRJNA1301834 | ENA

MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines [tempus]

2025-08-29 | GSE304583 | GEO

MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines [tempus]

Project description:MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines [tempus]

| PRJNA1301831 | ENA

MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-08-29 | GSE304585 | GEO

Identification of Biomarkers of Vaccine Reactogenicity

Project description:Systems vaccinology approaches have been used to successfully define early signatures of the vaccine-induced immune response. However, the possibility that transcriptomics can also predict vaccine reactogenicity has not been fully explored. We have compared four licensed vaccines that have a demonstrated safety profile, as well as three agonists of TLRs that have a known inflammatory potential, to elucidate the transcriptomic profile of an acceptable response to a vaccination versus those which push the inflammatory envelope. In mice, we looked at the transcriptomic changes in the injected muscle, the lymph node that drained the muscle and the PBMC isolated from the circulating blood from the very early timepoint of 4 hours to over the period of one week. A detailed examination and comparative analysis of the transcriptome from each of these tissues, at all the timepoints of 4, 8, 24, 48, 72 and 168 hr and with these eight different vaccines, TLR or saline control injections, revealed a set of novel biomarkers that are reflective of inflammation after vaccination. These biomarkers are easily sampled and readily measurable in the peripheral blood, providing a useful tool to predict levels of reactogenicity, as a way to select candidates with acceptable immunogenicity and safety profiles.

2019-01-31 | GSE120661 | GEO

Gene expression profiles of MAIT cells, MAIT-iPSCs, hiPSCs, hESCs, and reMAIT cells

Project description:To show the similarity among MAIT-iPSCs, hiPSCs and hESCs and the gradual change of global gene expression of reMAIT cells along with differentiation, this experiment was designed. MAIT cells, MAIT-iPSCs, hiPSCs, hESCs, MAIT cells, and reMAIT cells at the several differerent stages of differentiation were collected. Then, they were applied in this experiment.

2013-03-21 | E-GEOD-44559 | biostudies-arrayexpress

A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA (BNT162b2/mRNA-1273) and adenovirus vectored vaccines (ChAdOx1-S)

Project description:We longitudinally profiled plasma proteomes in 54 adults vaccinated with the BNT162b2 (Pfizer-BioNTech) or ChAdOx1-S (Oxford-AstraZeneca) vaccines. Blood was collected pre-vaccination (V0) and 1-7 days after the 1st doses (BNT162b2 or mRNA-1273, V1) to assess innate and early adaptive responses. We identified key differences in the immune responses induced by the ChAdOx1-S and BNT162b2 vaccines that were correlated with subsequent antigen-specific antibody and T cell responses or vaccine reactogenicity. We observed that vaccination with ChAdOx1-S but not BNT162b2 induced a memory-like response after the first dose, which was correlated with the expression of several proteins involved in complement and coagulation. The COVID-19 Vaccine Immune Responses Study (COVIRS) thus represents a major resource to understand the immunogenicity and reactogenicity of these COVID-19 vaccines.

2023-03-01 | PXD036608 | Pride

Microarray expression profiling of NKT and MAIT subsets in different organs of B6-MAIT/CAST mice.

Project description:MAIT cells (MAITs) represent an abundant T lymphocyte subset with unique specificity for microbial metabolites presented by the MHC-1b molecule, MR1. MAIT conservation along evolution indicates important, non-redundant functions, but their low frequency in mice has hampered their detailed characterization. Here, we performed a transcriptomic analysis of murine MAITs in comparison with NKT subsets and with mainstream T cells in spleen and peripheral organs of B6-MAIT/CAST mice expressing a Rorc-GFP transgene. MAIT and NKT cells have been FACS-sorted after tetramer staining (MR1:5-OP-RU Tet+ for MAIT, CD1d:PBS57Tet+ for NKT), and 1/17 subsetting based on the expression of Rorc.

2018-12-03 | E-MTAB-7133 | biostudies-arrayexpress

MAIT cell activation augments adenovirus vector vaccine immunogenicity

Project description:Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses, which can augment early immune responses and contribute to protection from lethal infection. Thus, we reasoned MAIT cells may have an adjuvating role in the immunogenicity of replication-incompetent adenovirus vectors, which are novel vaccine platforms for pandemic pathogens such as Ebola virus and SARS-CoV-2. In both mice and human volunteers, immunization with ChAdOx1 (Chimpanzee Adenovirus Ox1) robustly activated MAIT cells. Activation required transduction of plasmacytoid dendritic cells and monocytes to produce IFN- and IL-18, respectively. IFN--induced monocyte-derived TNF was identified as a novel intermediate in this activation pathway, and activation required combinatorial signaling of all three cytokines both in vitro and in vivo. Strikingly, vaccine-induced activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers. Supporting a causal relationship, MAIT cell-deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. These findings define a novel role for MAIT cells in the immunogenicity of adenovirus vector vaccines, with potential implications for vaccine design.

2020-10-01 | GSE158835 | GEO

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