Blood transcriptional correlates of BCG-induced protection against tuberculosis in rhesus macaques.
Cell Rep Med
; 4(7): 101096, 2023 07 18.
Article
em En
| MEDLINE
| ID: mdl-37390827
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Mycobacterium tuberculosis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell Rep Med
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos