A comprehensive approach to developing a multi-epitope vaccine against Mycobacterium tuberculosis : from in silico design to in vitro immunization evaluation

• Published in: Frontiers in immunology Vol. 14; p. 1280299
• Main Authors: Jiang, Fan, Han, Yong, Liu, Yinping, Xue, Yong, Cheng, Peng, Xiao, Li, Gong, Wenping
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2023
• Subjects: BCG Vaccine; Cytokines; cytometric bead assay (CBA); enzyme linked immunospot assay (ELISPOT); Epitopes, T-Lymphocyte; Humans; Immunization; immunoinformatic; multi-epitope vaccine (MEV); Mycobacterium tuberculosis; Mycobacterium tuberculosis (MTB); tuberculosis (TB); Tuberculosis - prevention & control; cytometric bead assay (CBA); multi-epitope vaccine (MEV); immunoinformatic; Mycobacterium tuberculosis (MTB); enzyme linked immunospot assay (ELISPOT); tuberculosis (TB)
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1280299

The Bacillus Calmette-Guérin (BCG) vaccine, currently used against tuberculosis (TB), exhibits inconsistent efficacy, highlighting the need for more potent TB vaccines. In this study, we employed reverse vaccinology techniques to develop a promising multi-epitope vaccine (MEV) candidate, called PP13138R, for TB prevention. PP13138R comprises 34 epitopes, including B-cell, cytotoxic T lymphocyte, and helper T lymphocyte epitopes. Using bioinformatics and immunoinformatics tools, we assessed the physicochemical properties, structural features, and immunological characteristics of PP13138R. The vaccine candidate demonstrated excellent antigenicity, immunogenicity, and solubility without any signs of toxicity or sensitization. analyses revealed that PP13138R interacts strongly with Toll-like receptor 2 and 4, stimulating innate and adaptive immune cells to produce abundant antigen-specific antibodies and cytokines. experiments further supported the efficacy of PP13138R by significantly increasing the population of IFN-γ T lymphocytes and the production of IFN-γ, TNF-α, IL-6, and IL-10 cytokines in active tuberculosis patients, latent tuberculosis infection individuals, and healthy controls, revealing the immunological characteristics and compare the immune responses elicited by the PP13138R vaccine across different stages of infection. These findings highlight the potential of PP13138R as a promising MEV candidate, characterized by favorable antigenicity, immunogenicity, and solubility, without any toxicity or sensitization.