Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303709 | PMC |
| http://dx.doi.org/10.7774/cevr.2025.14.e21 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Advancing the fight against tuberculosis: integrating innovation and public health in diagnosis, treatment, vaccine development, and implementation science.
Front Med (Lausanne)
August 2025
Department of Pathology and Laboratory Diagnosis, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia.
Tuberculosis (TB) remains one of the leading causes of infectious disease mortality worldwide, increasingly complicated by the emergence of drug-resistant strains and limitations in existing diagnostic and therapeutic strategies. Despite decades of global efforts, the disease continues to impose a significant burden, particularly in low- and middle-income countries (LMICs) where health system weaknesses hinder progress. This comprehensive review explores recent advancements in TB diagnostics, antimicrobial resistance (AMR surveillance), treatment strategies, and vaccine development.
View Article and Find Full Text PDFMultilevel systems biology analysis identifies key immune response profiles and potential correlates of protection for M72/AS01E vaccine against tuberculosis.
Clin Exp Vaccine Res
July 2025
Department of Chemical Sciences, Crescent University, Abeokuta, Nigeria.
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.
View Article and Find Full Text PDFThe PE/PPE family proteins of : evolution, function, and prospects for tuberculosis control.
Front Immunol
August 2025
Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Tuberculosis (TB), caused by (Mtb), remains a leading global health threat, exacerbated by drug resistance and inadequate vaccine efficacy. The PE/PPE protein family, unique to mycobacteria, constitutes ~10% of the Mtb genome and plays critical roles in bacterial physiology, immune evasion, and host-pathogen interactions. This review synthesizes advances in understanding the evolutionary expansion, structural diversity, and functional versatility of PE/PPE proteins, emphasizing their co-evolution with type VII secretion systems (T7SS).
View Article and Find Full Text PDFPPE18 and PepA Variations in Mycobacterium tuberculosis Clinical Isolates from Makassar, Indonesia: Challenges for Immune Recognition and Vaccine Development.
Int J Mycobacteriol
April 2025
Centre for Vaccine and Drugs Research, Health Research Organization, National Research and Innovation Agency (BRIN), Banten, Indonesia.
Background: The M72/AS01E tuberculosis vaccine candidate, currently on trial in Indonesia, includes PPE18 (Rv1196) and PepA (Rv0125) as key antigens. Genetic variation in these proteins may affect immune recognition and vaccine efficacy. This study aims to analyse the genetic diversity of Rv1196 and Rv0125 in Mycobacterium tuberculosis clinical isolates from Indonesia and assess the structural and immunological implications using in silico methods.
View Article and Find Full Text PDFThe critical role of new tuberculosis vaccines in achieving the WHO 2035 End TB target.
IJID Reg
March 2025
College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia.
This perspective article, in recognition of World TB Day 2025, highlights the essential role that new tuberculosis (TB) vaccines play in meeting the World Health Organization's goal of ending TB by 2035. The article does not provide a comprehensive review of all vaccine candidates but emphasizes the urgent need for novel TB vaccines, given the limitations of the bacillus Calmette-Guérin vaccine and the increasing threat of drug-resistant strains. As TB continues to be a leading cause of global morbidity and mortality, with an estimated 10.
View Article and Find Full Text PDF