An Immunoinformatics-Based Study of Mycobacterium tuberculosis Region of Difference-2 Uncharacterized Protein (Rv1987) as a Potential Subunit Vaccine Candidate for Preliminary Ex Vivo Analysis

Mycobacterium tuberculosis (Mtb) is the pathogen that causes tuberculosis and develops resistance to many of the existing drugs. The sole licensed TB vaccine, BCG, is unable to provide a comprehensive defense. So, it is crucial to maintain the immunological response to eliminate tuberculosis. Our pr...

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Published in:Applied biochemistry and biotechnology 2024-04, Vol.196 (4), p.2367-2395
Main Authors: Arega, Aregitu Mekuriaw, Dhal, Ajit Kumar, Pattanaik, Kali Prasad, Nayak, Sasmita, Mahapatra, Rajani Kanta
Format: Article
Language:English
Subjects:
Animal models
Animals
Antigens
Antigens, Bacterial - chemistry
Antigens, Bacterial - genetics
Antigens, Bacterial - immunology
Bacillus Calmette-Guerin vaccine
Bacterial Proteins - chemistry
Bacterial Proteins - genetics
Bacterial Proteins - immunology
BCG
Biochemistry
Biotechnology
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Chemistry
Chemistry and Materials Science
Computational Biology
Epitopes
Epitopes, B-Lymphocyte - immunology
Gene expression
Humans
Immune response
Immune system
Immunogenicity
Immunoinformatics
Immunology
Immunosuppressive agents
Lymphocytes B
Lymphocytes T
Macrophages
Major histocompatibility complex
Mass spectrometry
Mass spectroscopy
Mice
Molecular Docking Simulation
Mycobacterium tuberculosis
Mycobacterium tuberculosis - immunology
Nucleotide sequence
Original Article
Peptides
Protein structure
Proteins
Three dimensional models
Toll-Like Receptor 4 - immunology
Toll-Like Receptor 4 - metabolism
Tuberculosis
Tuberculosis - immunology
Tuberculosis - prevention & control
Tuberculosis Vaccines - immunology
Tumor necrosis factor-α
Vaccines
Vaccines, Subunit - immunology
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Summary:Mycobacterium tuberculosis (Mtb) is the pathogen that causes tuberculosis and develops resistance to many of the existing drugs. The sole licensed TB vaccine, BCG, is unable to provide a comprehensive defense. So, it is crucial to maintain the immunological response to eliminate tuberculosis. Our previous in silico study reported five uncharacterized proteins as potential vaccine antigens. In this article, we considered the uncharacterized Mtb H37Rv regions of difference (RD-2) Rv1987 protein as a promising vaccine candidate. The vaccine quality of the protein was analyzed using reverse vaccinology and immunoinformatics-based quality-checking parameters followed by an ex vivo preliminary investigation. In silico analysis of Rv1987 protein predicted it as surface localized, secretory, single helix, antigenic, non-allergenic, and non-homologous to the host protein. Immunoinformatics analysis of Rv1987 by CD4 + and CD8 + T-cells via MHC-I and MHC-II binding affinity and presence of B-cell epitope predicted its immunogenicity. The docked complex analysis of the 3D model structure of the protein with immune cell receptor TLR-4 revealed the protein’s capability for potential interaction. Furthermore, the target protein-encoded gene Rv1987 was cloned, over-expressed, purified, and analyzed by mass spectrometry (MS) to report the target peptides. The qRT-PCR gene expression analysis shows that it is capable of activating macrophages and significantly increasing the production of a number of key cytokines (TNF-α, IL-1β, and IL-10). Our in-silico analysis and ex vivo preliminary investigations revealed the immunogenic potential of the target protein. These findings suggest that the Rv1987 be undertaken as a potent subunit vaccine antigen and that further animal model immuno-modulation studies would boost the novel TB vaccine discovery and/or BCG vaccine supplement pipeline.
ISSN:0273-2289
1559-0291
DOI:10.1007/s12010-023-04658-9