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Blood transcriptional correlates of BCG-induced protection against tuberculosis in rhesus macaques
Blood-based correlates of vaccine-induced protection against tuberculosis (TB) are urgently needed. Here, we analyze the blood transcriptome of rhesus macaques immunized with varying doses of intravenous (i.v.) BCG followed by Mycobacterium tuberculosis (Mtb) challenge. We use high-dose i.v. BCG rec...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394165/ https://www.ncbi.nlm.nih.gov/pubmed/37390827 http://dx.doi.org/10.1016/j.xcrm.2023.101096 |
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author | Liu, Yiran E. Darrah, Patricia A. Zeppa, Joseph J. Kamath, Megha Laboune, Farida Douek, Daniel C. Maiello, Pauline Roederer, Mario Flynn, JoAnne L. Seder, Robert A. Khatri, Purvesh |
author_facet | Liu, Yiran E. Darrah, Patricia A. Zeppa, Joseph J. Kamath, Megha Laboune, Farida Douek, Daniel C. Maiello, Pauline Roederer, Mario Flynn, JoAnne L. Seder, Robert A. Khatri, Purvesh |
author_sort | Liu, Yiran E. |
collection | PubMed |
description | Blood-based correlates of vaccine-induced protection against tuberculosis (TB) are urgently needed. Here, we analyze the blood transcriptome of rhesus macaques immunized with varying doses of intravenous (i.v.) BCG followed by Mycobacterium tuberculosis (Mtb) challenge. We use high-dose i.v. BCG recipients for “discovery” and validate our findings in low-dose recipients and in an independent cohort of macaques receiving BCG via different routes. We identify seven vaccine-induced gene modules, including an innate module (module 1) enriched for type 1 interferon and RIG-I-like receptor signaling pathways. Module 1 on day 2 post-vaccination highly correlates with lung antigen-responsive CD4 T cells at week 8 and with Mtb and granuloma burden following challenge. Parsimonious signatures within module 1 at day 2 post-vaccination predict protection following challenge with area under the receiver operating characteristic curve (AUROC) ≥0.91. Together, these results indicate that the early innate transcriptional response to i.v. BCG in peripheral blood may provide a robust correlate of protection against TB. |
format | Online Article Text |
id | pubmed-10394165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-103941652023-08-03 Blood transcriptional correlates of BCG-induced protection against tuberculosis in rhesus macaques Liu, Yiran E. Darrah, Patricia A. Zeppa, Joseph J. Kamath, Megha Laboune, Farida Douek, Daniel C. Maiello, Pauline Roederer, Mario Flynn, JoAnne L. Seder, Robert A. Khatri, Purvesh Cell Rep Med Article Blood-based correlates of vaccine-induced protection against tuberculosis (TB) are urgently needed. Here, we analyze the blood transcriptome of rhesus macaques immunized with varying doses of intravenous (i.v.) BCG followed by Mycobacterium tuberculosis (Mtb) challenge. We use high-dose i.v. BCG recipients for “discovery” and validate our findings in low-dose recipients and in an independent cohort of macaques receiving BCG via different routes. We identify seven vaccine-induced gene modules, including an innate module (module 1) enriched for type 1 interferon and RIG-I-like receptor signaling pathways. Module 1 on day 2 post-vaccination highly correlates with lung antigen-responsive CD4 T cells at week 8 and with Mtb and granuloma burden following challenge. Parsimonious signatures within module 1 at day 2 post-vaccination predict protection following challenge with area under the receiver operating characteristic curve (AUROC) ≥0.91. Together, these results indicate that the early innate transcriptional response to i.v. BCG in peripheral blood may provide a robust correlate of protection against TB. Elsevier 2023-06-29 /pmc/articles/PMC10394165/ /pubmed/37390827 http://dx.doi.org/10.1016/j.xcrm.2023.101096 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Yiran E. Darrah, Patricia A. Zeppa, Joseph J. Kamath, Megha Laboune, Farida Douek, Daniel C. Maiello, Pauline Roederer, Mario Flynn, JoAnne L. Seder, Robert A. Khatri, Purvesh Blood transcriptional correlates of BCG-induced protection against tuberculosis in rhesus macaques |
title | Blood transcriptional correlates of BCG-induced protection against tuberculosis in rhesus macaques |
title_full | Blood transcriptional correlates of BCG-induced protection against tuberculosis in rhesus macaques |
title_fullStr | Blood transcriptional correlates of BCG-induced protection against tuberculosis in rhesus macaques |
title_full_unstemmed | Blood transcriptional correlates of BCG-induced protection against tuberculosis in rhesus macaques |
title_short | Blood transcriptional correlates of BCG-induced protection against tuberculosis in rhesus macaques |
title_sort | blood transcriptional correlates of bcg-induced protection against tuberculosis in rhesus macaques |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394165/ https://www.ncbi.nlm.nih.gov/pubmed/37390827 http://dx.doi.org/10.1016/j.xcrm.2023.101096 |
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