Related Experiment Video
Updated: Sep 13, 2025
Author Spotlight: Optimizing CFU Determination for Efficient Assessment of TB Vaccine Efficacy and Antigen Presentation Analysis
Published on: July 28, 2023
Multilevel systems biology analysis identifies key immune response profiles and potential correlates of protection
Oluwaseun Oluwatosin Taofeek1, Solomon Osarumwense Alile2, Elcanah Mauta Evans3
1Department 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. 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.
Related Concept Videos
01:31Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
01:51Vaccinations
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...