High-dose intravenous BCG vaccination induces enhanced immune signaling in the airways
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Joshua M. Peters, Edward B. Irvine, Jacob M. Rosenberg, Marc H. Wadsworth II, Travis K. Hughes, Matthew Sutton, Sarah K. Nyquist, Joshua D. Bromley, Rajib Mondal, Mario Roederer, Robert A. Seder, Patricia A. Darrah, Galit Alter, JoAnne L. Flynn, Alex K. Shalek, Sarah M. Fortune, Bryan D. Bryson
DOI: https://www.science.org/doi/10.1126/sciadv.adq8229
Intradermal Bacillus Calmette-Guérin (BCG) is the most widely administered vaccine, but it does not sufficiently protect adults against pulmonary tuberculosis. Recent studies in nonhuman primates show that intravenous BCG administration offers superior protection against Mycobacterium tuberculosis (Mtb). We used single-cell analysis of bronchoalveolar lavage cells from rhesus macaques vaccinated via different routes and doses of BCG to identify alterations in the immune ecosystem in the airway following vaccination. Our findings reveal that high-dose intravenous BCG induces an influx of polyfunctional T cells and macrophages in the airways, with alveolar macrophages from high-dose intravenous BCG displaying a basal activation state in the absence of purified protein derivative stimulation, defined in part by interferon signaling. Enhanced intercellular immune signaling and stronger T helper 1–T helper 17 transcriptional responses were observed following purified protein derivative stimulation. These results suggest that high-dose intravenous BCG vaccination creates a specialized immune environment that primes airway cells for effective Mtb clearance.
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Created: 7th Mar 2023 at 17:33
Last updated: 6th Jan 2025 at 19:59
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Projects: MIT SRP, Hi-IMPAcTB, MetNet, Endometriosis, Cancer Systems Biology Consortium (CSBC), Shoulders Lab, NExtSEEK Independent Projects
Web page: https://nextseek.mit.edu/
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This project houses all the publicly available datasets generated by the Hi-IMPAcTB consortium over the course of its 7+ years.
What is Hi-IMPAcTB?
Hi-IMPAcTB is an ambitious endeavor bringing together a team of international, interdisciplinary researchers to improve our understanding of host-pathogen interactions in the context of tuberculosis (TB). Funded by a multi-center contract from the NIH, the long-term goal of the consortium is to enable principled vaccine design by improving ...
Programme: NExtSEEK
Public web page: https://grantome.com/grant/NIH/75N93019C00071-0-9999-1
Submitter: Dikshant Pradhan
Studies: Age and sex influence antibody profiles associated with tuberculosis pro..., Antibody-Fab and -Fc features promote Mycobacterium tuberculosis restric..., BCG vaccination elicits protection against Mtb infection mediated by two..., BCG vaccination induces antibacterial effector functions among Vδ1/3 T c..., CD4+ T cells re-wire granuloma cellularity and regulatory networks to pr..., CD8+ lymphocytes are critical for early control of tuberculosis in macaques, Comparable Non-canonical T cell responses are associated with protection..., Fc-engineered antibodies promote neutrophil-dependent control of Mycobac..., Fc-engineered monoclonal antibodies drive antibody-dependent enhancement..., Fc-engineered monoclonal antibodies drive antibody-dependent enhancement..., High-dose intravenous BCG vaccination induces enhanced immune signaling ..., Humoral correlates of protection against Mycobacterium tuberculosis foll..., IFN-γ- GranzymeB + Natural killer cells are induced by IV BCG vaccinatio..., Immune cells in bronchoalveolar lavage fluid of Ugandan adults who resis..., Intravenous BCG-mediated protection against tuberculosis requires CD4+ T..., Multi-modal data integration using Markov Field graphical networks predi..., Multimodal profiling of lung granulomas in macaques reveals cellular cor..., Population-level genome sequencing reveals distinct Mycobacterium tuberc..., Protection against disseminated disease following reinfection with Mycob..., Protection against reinfection with Mycobacterium tuberculosis extends a..., Robust IgM responses following intravenous vaccination with Bacille Calm..., Soloman placeholder, Specific CD4+ T cell phenotypes associate with bacterial control in peop..., Systematic deconstruction of myeloid cell signaling in tuberculosis gran..., Systems-level computational translation of mouse and human transcriptomi...
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Data Linked, ELISA Assay - Data Linked, FC Receptor Binding - Data Linked, FC Receptor Binding Analysis - Data Linked, FC Receptor Binding Assay - Data Linked, FC-Receptor Binding Assay - Data Linked, FCS Analysis - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry - Data Linked, Flow Cytometry Analysis - Data Attached, Flow Cytometry Analysis - Data Linked, Flow Cytometry Analysis - Data Linked, Flow Cytometry Analysis - Data Linked, Flow Cytometry Analysis - Data Linked, Flow Cytometry Analysis - Data Linked, Flow Cytometry Analysis - Data Linked, Flow Cytometry Analysis - Data Linked, Flow Cytometry Analysis - Data Linked, Flow Cytometry Processing – Data Attached, Flow Cytometry – Data Linked, Functional Assay – Metadata, Gene Expression Analysis - Data Linked, Gene Expression Analysis: Training Data - Data Linked, Gene Expression Analysis: Validation Data - Data Linked, Glycosylation Assay - Data Linked, Histology - Data Linked, Immunohistochemistry - Data Linked, Immunohistochemistry - Data Linked, Immunohistochemistry – Data Linked, Library Collection - Metadata, Library Creation - Metadata, Library Creation - Metadata, Library Creation - Metadata, Library Creation – Metadata, Library Prep - Metadata, Library Prep - Metadata, Library Prep - Metadata, Library Prep - Metadata, Library Prep - Metadata, Library Prep: Training Data - Metadata, Library Prep: Validation Data - Metadata, Linear Mixed Model - Data Linked, Luminex - Data Linked, Luminex Assay – Metadata, Luminex Data Processing – Data Attached, Mass Cytometry - Data Linked, Mass Cytometry - Data Linked, Mass Cytometry Analysis - Data Linked, Model Validation, Model Validation - Data Linked, Mouse Challenge – Metadata, NHP Necropsy – Metadata, NHP Tissue Collection – Metadata, PCR: Validation Data - Data Attached, PET-CT Scan - Data Linked, PET-CT Scan - Data Linked, PET-CT Scan - Data Linked, PET-CT Scan Analysis – Data Linked, PET-CT Scan – Data Linked, PET/CT Scan - Data Linked, PET/CT Scan - Data Linked, Pathogen Challenge and Antibody Depletion - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit - Metadata, Patient Visit – Metadata, Patient Visit – Metadata, RNA Extraction: Validation Data - Metadata, Short Read Sequencing - Data Linked, Short Read Sequencing - Data Linked, Short Read Sequencing - Data Linked, Short Read Sequencing - Data Linked, Short Read Sequencing - Data Linked, Short Read Sequencing - Data Linked, Short Read Sequencing - Data Linked, Short Read Sequencing - 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