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Series GSE139598 Query DataSets for GSE139598
Status Public on Jan 01, 2020
Title Prevention of Mycobacterium tuberculosis infection and disease in nonhuman primates following intravenous BCG vaccination
Organism Macaca mulatta
Experiment type Expression profiling by high throughput sequencing
Summary Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide. Intradermal (ID) vaccination with BCG has variable efficacy against pulmonary tuberculosis, the major cause of mortality and disease transmission. Here we show that the route and dose of BCG vaccination alters circulating and lung resident T cells and subsequent protection against Mtb challenge in nonhuman primates (NHP). NHP immunized with BCG by the intravenous (IV) route induced substantially higher antigen-specific CD4 (Th1 or Th17) and CD8 responses in blood, spleen, bronchoalveolar lavage (BAL), and lung lymph nodes compared to the same BCG dose administered by ID or aerosol (AE) routes. Moreover, IV immunization was the only route that induced a high frequency of antigen-specific tissue resident T cells in lung parenchyma. Six months after BCG vaccination, NHP were challenged with virulent Mtb. Strikingly, 9 of 10 NHP that received BCG IV were highly protected, with 6 NHP showing no detectable infection as determined by PET CT imaging, mycobacterial growth, pathology, granuloma formation, or de novo immune responses to Mtb-specific antigens. The finding that BCG IV prevents or significantly limits Mtb infection in NHP has important implications for vaccine development and provides a model for determining immune correlates and mechanisms of protection against TB.
Overall design Single-cell RNA-Sequencing of Bronchoalveolar Lavages from animals vaccinated using different routes and doses of BCG
Contributor(s) Darrah PA, Zeppa JJ, Hackney JA, Wadsworth II MH, Hughes TK, Pokkali S, Swanson PA, Grant NL, Rodgers MA, Scanga CA, Causgrove CM, Laddy DJ, Bonavia A, Casimiro D, Lin PL, Klein E, Maiello P, Shalek AK, Roederer M, Flynn J, Seder RA
Citation(s) 31894150
Submission date Oct 30, 2019
Last update date Jan 03, 2020
Contact name Alex Shalek
Organization name MIT
Department Chemistry
Lab Shalek Lab
Street address 45 Carleton Street
City Cambridge
State/province MA
ZIP/Postal code 02139
Country USA
Platforms (1)
GPL21120 Illumina NextSeq 500 (Macaca mulatta)
Samples (60)
GSM4144370 Week13_unstimulated_DF16_IDLow
GSM4144371 Week13_unstimulated_DFF3_IV
GSM4144372 Week13_unstimulated_DF8P_AE
BioProject PRJNA580456
SRA SRP227486

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Supplementary file Size Download File type/resource
GSE139598_Week13.All.Cells.Metadata.csv.gz 4.3 Mb (ftp)(http) CSV
GSE139598_Week13_Stimulated.Cells.UMI.collapsed.csv.gz 211.4 Mb (ftp)(http) CSV
GSE139598_Week13_Unstimulated.Cells.UMI.collapsed.csv.gz 211.4 Mb (ftp)(http) CSV
GSE139598_Week25.All.Cells.Metadata.csv.gz 2.9 Mb (ftp)(http) CSV
GSE139598_Week25_Stimulated.Cells.UMI.collapsed.csv.gz 118.4 Mb (ftp)(http) CSV
GSE139598_Week25_Unstimulated.Cells.UMI.collapsed.csv.gz 118.4 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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