Related Experiment Video
Updated: Sep 18, 2025
Enrichment of Native and Recombinant Extracellular Vesicles of Mycobacteria
Published on: December 8, 2023
PPE18 and PepA Variations in Mycobacterium tuberculosis Clinical Isolates from Makassar, Indonesia: Challenges for
Stephanie Cynthia Theorupun1, Muhammad Nasrum Massi1,2, Astutiati Nurhasanah3
1Department of Microbiology, Faculty of Medicine, Hasanuddin University, Makassar, 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.
Methods:
Rv1196 and Rv0125 genes from clinical isolates were sequenced and analysed for polymorphisms. PPE18 variants were modelled using I-TASSER (Iterative Threading ASSEmbly Refinement), and structural stability and HLA (Human Leukocyte Antigen) binding predictions (HLA-I and HLA-II) were performed using IEDB (Immune Epitope Database) tools. Molecular docking with TLR2 (Toll-like Receptor 2) was conducted to evaluate receptor interactions.
Results:
A novel non-synonymous mutation (T22G, Ser8Ala) was identified in Rv0125, which was otherwise conserved. Rv1196 showed high variability with 58 polymorphic sites, including 38 non-synonymous mutations, a frequent Arg287Gln substitution, and a ΔThr163-Ala164 deletion. Structural modelling indicated preserved PPE18 fold but altered epitope binding in an allele-specific manner. Docking showed stronger TLR2 interactions for variants 6S31 and 6S32, suggesting enhanced IL-10 induction and a Th2-skewed immune response.
Conclusions:
PPE18 genetic variation may influence immune recognition and the effectiveness of M72/AS01E. Ongoing antigenic surveillance in endemic areas is essential to guide vaccine design and diagnostics.
Insights
Genetic variations in tuberculosis vaccine antigens PPE18 and PepA were analyzed in Indonesian isolates. PPE18 showed significant diversity, potentially impacting M72/AS01E vaccine efficacy and immune response.
Area of Science:
- * Molecular biology and immunology
- * Vaccine development and efficacy studies
Background:
- * The M72/AS01E tuberculosis vaccine candidate utilizes PPE18 (Rv1196) and PepA (Rv0125) antigens.
- * Genetic diversity in these antigens may influence immune recognition and vaccine effectiveness.
Purpose of the Study:
- * To analyze the genetic diversity of Rv1196 and Rv0125 in Indonesian Mycobacterium tuberculosis clinical isolates.
- * To assess the structural and immunological implications of identified genetic variations using in silico methods.
Main Methods:
- * Sequencing of Rv1196 and Rv0125 genes from clinical isolates.
- * In silico analysis including protein structure modeling (I-TASSER), HLA binding predictions (IEDB), and molecular docking with TLR2.
Main Results:
- * Rv0125 exhibited a novel non-synonymous mutation (Ser8Ala), while Rv1196 displayed high variability with 58 polymorphic sites and a common Arg287Gln substitution.
- * Structural modeling revealed preserved PPE18 fold but altered, allele-specific epitope binding.
- * Docking simulations indicated stronger TLR2 interactions for certain PPE18 variants, suggesting potential for enhanced IL-10 induction and a Th2-skewed immune response.
Conclusions:
- * Genetic variation in PPE18 may impact immune recognition and the efficacy of the M72/AS01E vaccine.
- * Continuous antigenic surveillance in endemic regions is crucial for optimizing tuberculosis vaccine design and diagnostics.
More Related Videos
06:26Author Spotlight: Optimizing CFU Determination for Efficient Assessment of TB Vaccine Efficacy and Antigen Presentation Analysis
Published on: July 28, 2023
10:11Expression of Exogenous Antigens in the Mycobacterium bovis BCG Vaccine via Non-genetic Surface Decoration with the Avidin-biotin System
Published on: January 31, 2018
Related Concept Videos
01:29Pulmonary Tuberculosis I
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
01:28Pulmonary Tuberculosis II
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...
01:28Pulmonary Tuberculosis V
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
01:31Pulmonary Tuberculosis III
The first classification is based on the development of the disease, and it includes the following categories:
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...
01:26Pulmonary Tuberculosis IV
Several diagnostic approaches are used to detect TB. The conventional method is the Tuberculin Skin Test (TST), also known as the Mantoux test. However, this method has...