ArticleClinical and experimental vaccine research2025
Multilevel systems biology analysis identifies key immune response profiles and potential correlates of protection for M72/AS01E vaccine against tuberculosis.
Article in Clinical and experimental vaccine research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Bacillus Calmette-Guérin (BCG) Vaccination and the Immune-Brain Axis: Implications for Neuroprotection and Neurodegenerative Disease.Vaccines · 2026Review
- Host-directed microRNA-based intervention against intracellularFrontiers in cellular and infection microbiology · 2026Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Tuberculosis (TB) claims around 1.5 million lives annually. The M72/AS01E vaccine candidate is an innovative effort demonstrating a 50% reduction in the incidence of active TB in adults. However, optimization and effective immunization strategies against TB depends heavily on precise identification of specific molecular signatures active in vaccine protection. Materials and Methods: In this study, we employed weighted gene co-expression network analysis, machine learning, and network biology to investigate the gene expression patterns of peripheral blood mononuclear cells, identifying transcriptomic markers of vaccine protection. Results: Our comprehensive exploration of publicly available gene expression dataset comprising samples from subjects vaccinated twice with 10 μg of M72/AS01E vaccine one day post-second dose (D31) and one week post-second dose (D37) in a phase IIA clinical trial revealed intense induction of multiple gene modules, indicative of acute/immediate immune response at D31 that subsided by D37. Thirty-one hub genes with significant elevation/correlation with immune protection were identified significantly mediating key events in immunity to TB. The more selective profile at D37 involved additional adaptive immunity pathways including T helper (Th) 1/Th2/Th17 differentiation, T cell receptor and cytokine signaling. The functional relevance of these biomarkers in predicting vaccine response was further analyzed using the Random Forest classifier demonstrating high accuracy in distinguishing between vaccinated and non-vaccinated samples. Additionally, the study pinpointed a miRNAs-transcription factors (TF)-target regulatory network excavating key TF, miRNA, mRNAs mediating vaccine protection. Conclusion: Our results provided new insights into M72/AS01E immunity, warranting further study to optimize and guide future TB vaccine development.
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