Protective heterologous T cell immunity in COVID-19 induced by MMR and Tdap vaccine antigens
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PROVIDER: PRJNA750464 | ENA |
REPOSITORIES: ENA
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Project description:High correlation was observed between T cell responses to SARS-CoV-2 and MMR and Tdap vaccine proteins in infected and uninfected individuals; the overlapping T cell population contained an effector memory T cell subset previously implicated in protective anti-viral immunity and their activation required APC-derived IL-15, known to sensitize T cells to activation. We were able to detect cross-reactive TCR repertoire in antigen experienced T cells recognizing SARS-CoV-2, MMR and Tdap epitopes using clonotyping and scRNA-seq. Indices of disease severity were reduced in MMR or Tdap vaccinated individuals by 32-38% and 20-23% respectively, among 73.582 COVID-19 positive patients.
2021-08-02 | GSE181046 | GEO
Project description:BackgroundT cells control viral infection, promote vaccine durability, and in coronavirus disease 2019 (COVID-19) associate with mild disease. We investigated whether prior measles-mumps-rubella (MMR) or tetanus-diphtheria-pertussis (Tdap) vaccination elicits cross-reactive T cells that mitigate COVID-19.MethodsAntigen-presenting cells (APC) loaded ex vivo with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MMR, or Tdap antigens and autologous T cells from COVID-19-convalescent participants, uninfected individuals, and COVID-19 mRNA-vaccinated donors were co-cultured. T cell activation and phenotype were detected by interferon-γ (IFN-γ) enzyme-linked immunospot (ELISpot) assays and flow cytometry. ELISAs (enzyme-linked immunosorbant assays) and validation studies identified the APC-derived cytokine(s) driving T cell activation. TCR clonotyping and single-cell RNA sequencing (scRNA-seq) identified cross-reactive T cells and their transcriptional profile. A propensity-weighted analysis of COVID-19 patients estimated the effects of MMR and Tdap vaccination on COVID-19 outcomes.FindingsHigh correlation was observed between T cell responses to SARS-CoV-2 (spike-S1 and nucleocapsid) and MMR and Tdap proteins in COVID-19-convalescent and -vaccinated individuals. The overlapping T cell population contained an effector memory T cell subset (effector memory re-expressing CD45RA on T cells [TEMRA]) implicated in protective, anti-viral immunity, and their detection required APC-derived IL-15, known to sensitize T cells to activation. Cross-reactive TCR repertoires detected in antigen-experienced T cells recognizing SARS-CoV-2, MMR, and Tdap epitopes had TEMRA features. Indices of disease severity were reduced in MMR- or Tdap-vaccinated individuals by 32%-38% and 20%-23%, respectively, among COVID-19 patients.ConclusionsTdap and MMR memory T cells reactivated by SARS-CoV-2 may provide protection against severe COVID-19.FundingThis study was supported by a National Institutes of Health (R01HL065095, R01AI152522, R01NS097719) donation from Barbara and Amos Hostetter and the Chleck Foundation.
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Project description:Control of pertussis depends on primary vaccination of infants in combination with booster vaccination of children, adults, and recently also pregnant women. Tetanus-diptheria-acellular pertussis (Tdap) booster vaccines are frequently given in many countries and can be formulated with inactivated poliovirus (Tdap-IPV). Although Tdap-IPV provides clinical protection, both pertussis antibody levels and clinical protection decay shortly after vaccination. This highlights the need for a better understanding of the mechanisms of immunogenicity of aP-containing combination vaccines, which may explain the longevity of the antibody response to vaccination. In order to identify immune signatures that are induced by Tdap-IPV vaccination and which can be associated with humoral responses, we analyzed changes in gene expression.
2024-01-22 | GSE195625 | GEO
Project description:Control of pertussis depends on primary vaccination of infants in combination with booster vaccination of children, adults, and recently also pregnant women. Tetanus-diptheria-acellular pertussis (Tdap) booster vaccines are frequently given in many countries and can be formulated with inactivated poliovirus (Tdap-IPV). Although Tdap-IPV provides clinical protection, both pertussis antibody levels and clinical protection decay shortly after vaccination. This highlights the need for a better understanding of the mechanisms of immunogenicity of aP-containing combination vaccines, which may explain the longevity of the antibody response to vaccination. In order to identify immune signatures that are induced by Tdap-IPV vaccination and which can be associated with humoral responses, we analyzed changes in gene expression.
2024-01-22 | GSE233855 | GEO
Project description:Control of pertussis depends on primary vaccination of infants in combination with booster vaccination of children, adults, and recently also pregnant women. Tetanus-diptheria-acellular pertussis (Tdap) booster vaccines are frequently given in many countries and can be formulated with inactivated poliovirus (Tdap-IPV). Although Tdap-IPV provides clinical protection, pertussis antibody levels decay shortly after vaccination. This highlights the need for a better understanding of the mechanisms of immunogenicity of aP-containing combination vaccines, which may explain the longevity of the antibody response to vaccination. In order to identify immune signatures that are induced by Tdap-IPV vaccination and which may be associated with humoral responses, we analyzed changes in gene expression.
2024-01-22 | GSE195626 | GEO
Project description:Interferon gene therapy reprograms the leukemia microenvironment inducing protective immunity to multiple tumor antigens
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Project description:Immunomic screening of mice immune sera with different protection efficiencies against the whole P. yoelii 17X parasite proteome was performed to identify the repertoire of antigens recognized by those sera. The calculation of weighted scores reflecting the likelihood of protection of each antigens using five predictive criteria derived from immunomic and proteomic datasets, highlighted a priority list of protective antigens.
2019-02-15 | PXD010567 | Pride
Project description:Endometrial cancer had a relatively high prevalence of MMR deficiency. MMR-D/MSI-H endometrial cancer patients are suggested to be potential beneficiaries of PD-1/PD-L1 inhibitor therapy. Here, we explored the prognostic value of MSI subtype in endometrial cancer and its correlation with immune environment. Based on expression and clinical data of 78 POLE, 123 MSI and 299 Other EC samples from the TCGA-UCEC project, we found that the MSI tumors were identified more often in early stage, had a lower age, better patient survival, enriched CD8+ T cells, and regulatory T cells and less M2 macrophages and activated dendritic cells than the Other group, and shared a relatively similar expression profile with POLE group by differential analysis. In addition, we established the immune landscape of an MMR-D endometrial cancer tissue using unbiased single-cell RNA-seq analysis of 3371 cells. By immunohistochemistry analysis, we found that the MMR-D tumors showed a higher trend of CD20+ B cells infiltration. Our study might expand our understanding of the role of immune subsets in MSI endometrial carcinomas and provide guidance of immunotherapy for endometrial cancer.
2022-03-09 | GSE193430 | GEO
Project description:The immune response against tuberculosis relies, at least in part, on CD4+ T cells. Protective vaccines require the induction of antigen-specific CD4+ T cells via mycobacterial peptides presented by MHC class-II in infected macrophages. We have purified MHC class-I and MHC-II peptides and analysed them by mass spectrometry. We have successfully identified 97 mycobacterial peptides presented by MHC-II and 54 presented by MHC-I, from 76 and 41 antigens, respectively. The sequences of selected peptides were confirmed by spectral match validation and immunogenicity evaluated by IFN-gamma ELISpot against peripheral blood mononuclear cells from volunteers vaccinated with BCG, M.tb latently infected subjects or patients with tuberculosis disease. Three antigens were expressed in viral vectors, and evaluated as vaccine candidates alone or in combination in a murine aerosol M.tb challenge model. When delivered in combination, the three candidate vaccines conferred significant protection in the lungs and spleen compared with BCG alone, demonstrating proof-of-concept for this unbiased approach to identifying novel candidate antigens.
2020-01-08 | E-MTAB-8057 | biostudies-arrayexpress