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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1474346

In silico analysis for the development of multi-epitope vaccines against Mycobacterium tuberculosis

Provisionally accepted
Jin-Seung Yun Jin-Seung Yun 1A REUM KIM A REUM KIM 2Soo Min Kim Soo Min Kim 1Eunkyung Shin Eunkyung Shin 1Sang-Jun Ha Sang-Jun Ha 3Dokeun Kim Dokeun Kim 1Hye-Sook Jeong Hye-Sook Jeong 4*
  • 1 National Institute of Health, Chungbuk, Republic of Korea
  • 2 National Institute of Environmental Research, Incheon, Republic of Korea
  • 3 College of Life Science and Biotechnology, Yonsei University, Seoul, Seoul, Republic of Korea
  • 4 Korea National Institute of Health, Cheongju-si, Republic of Korea

The final, formatted version of the article will be published soon.

    As Bacille Calmette-Guérin (BCG) vaccine's effectiveness is limited to only children, the development of new tuberculosis (TB) vaccines is being studied using several platforms, and a novel TB vaccine that overcomes this limitation is required. In this study, we designed an effective multi-epitope vaccine against Mycobacterium tuberculosis using immunoinformatic analysis. First, we selected 11 highly antigenic proteins based on previous research: Ag85A, Ag85B, Ag85C, ESAT-6, MPT64, Rv2660c, TB10.4, HspX, GlfT2, Fas, and IniB. Among these antigens, 10 linear B-cell epitopes, 9 helper T-cell epitopes, and 16 cytotoxic T-cell epitopes were predicted to design the multi-epitope vaccine. To improve the immunogenicity of the candidate vaccine, three different adjuvants, griselimycin, human beta-defensin 3 (HBD3), and 50s ribosomal protein (50sRP), were attached with linker sequences to the vaccine model. The immunogenic, antigenic, allergenic, and physicochemical properties of the resulting designed multi-epitope vaccines were predicted in silico. Moreover, 3D structural modeling, refinement, and validation were used to select a model for further evaluation. Molecular docking analysis revealed a consistent and significant binding affinity of the candidate vaccine for toll-like receptors (TLRs), TLR-2, -3, and -4. Immune simulation performed using C-ImmSim demonstrated that three rounds of immunization with multi-epitope vaccines induced a high production of cytokines and immunoglobulins related with both cellular and humoral immune response. Moreover, we constructed vaccine candidate composed of 50sRP and evaluated its immunogenicity in a mouse model. Consequently, this in silico-engineered multi-epitope structure can elicit adaptive immune responses and represents a promising novel candidate for TB vaccine development.

    Keywords: tuberculosis (TB), peptide-based vaccine, molecular docking, Immunoinformatics analysis, Multi-epitope

    Received: 01 Aug 2024; Accepted: 24 Oct 2024.

    Copyright: © 2024 Yun, KIM, Kim, Shin, Ha, Kim and Jeong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hye-Sook Jeong, Korea National Institute of Health, Cheongju-si, Republic of Korea

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.