Discovering peptides and computational investigations of a multiepitope vaccine target Mycobacterium tuberculosis
Mycobacterium tuberculosis (MTB) is the causative agent of tuberculosis (TB), a prevalent airborne infectious disease. Despite the availability of the Bacille Calmette-Guerin vaccine, its global efficacy remains modest, and tuberculosis persists as a significant global public health threat. Addressi...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2024-09-01
|
| Series: | Synthetic and Systems Biotechnology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X24000449 |
| _version_ | 1797235542471999488 |
|---|---|
| author | Truc Ly Nguyen Heebal Kim |
| author_facet | Truc Ly Nguyen Heebal Kim |
| author_sort | Truc Ly Nguyen |
| collection | DOAJ |
| description | Mycobacterium tuberculosis (MTB) is the causative agent of tuberculosis (TB), a prevalent airborne infectious disease. Despite the availability of the Bacille Calmette-Guerin vaccine, its global efficacy remains modest, and tuberculosis persists as a significant global public health threat. Addressing this challenge and advancing towards the End MTB Strategy, we developed a multiepitope vaccine (MEV) based on immunoinformatics and computational approaches. Immunoinformatics screening of MBT protein identified immune-dominant epitopes based on Major Histocompatibility Complex (MHC) allele binding, immunogenicity, antigenicity, allergenicity, toxicity, and cytokine inducibility. Selected epitopes were integrated into an MEV construct with adjuvant and linkers, forming a fully immunogenic vaccine candidate. Comprehensive analyses encompassed the evaluation of immunological and physicochemical properties, determination of tertiary structure, molecular docking with Toll-Like Receptors (TLR), molecular dynamics (MD) simulations for all atoms, and immune simulations. Our MEV comprises 534 amino acids, featuring 6 cytotoxic T lymphocyte, 8 helper T lymphocyte, and 7 linear B lymphocyte epitopes, demonstrating high antigenicity and stability. Notably, molecular docking studies and triplicate MD simulations revealed enhanced interactions and stability of MEV with the TLR4 complex compared to TLR2. In addition, the immune simulation indicated the capacity to effectively induce elevated levels of antibodies and cytokines, emphasizing the vaccine's robust immunogenic response. This study presents a promising MEV against TB, exhibiting favorable immunological and physicochemical attributes. The findings provide theoretical support for TB vaccine development. Our study aligns with the global initiative of the End MTB Strategy, emphasizing its potential impact on addressing persistent challenges in TB control. |
| first_indexed | 2024-04-24T16:49:37Z |
| format | Article |
| id | doaj.art-7ccde9e93ffc4fe58d0ebc125c50b8e4 |
| institution | Directory Open Access Journal |
| issn | 2405-805X |
| language | English |
| last_indexed | 2024-04-24T16:49:37Z |
| publishDate | 2024-09-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Synthetic and Systems Biotechnology |
| spelling | doaj.art-7ccde9e93ffc4fe58d0ebc125c50b8e42024-03-29T05:50:33ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2024-09-0193391405Discovering peptides and computational investigations of a multiepitope vaccine target Mycobacterium tuberculosisTruc Ly Nguyen0Heebal Kim1Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of KoreaDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 08826, Republic of Korea; eGnome, Inc., Seoul, 05836, Republic of Korea; Corresponding author: Department of Agricultural Biotechnology, Seoul National University, Seoul, 08826, Republic of Korea.Mycobacterium tuberculosis (MTB) is the causative agent of tuberculosis (TB), a prevalent airborne infectious disease. Despite the availability of the Bacille Calmette-Guerin vaccine, its global efficacy remains modest, and tuberculosis persists as a significant global public health threat. Addressing this challenge and advancing towards the End MTB Strategy, we developed a multiepitope vaccine (MEV) based on immunoinformatics and computational approaches. Immunoinformatics screening of MBT protein identified immune-dominant epitopes based on Major Histocompatibility Complex (MHC) allele binding, immunogenicity, antigenicity, allergenicity, toxicity, and cytokine inducibility. Selected epitopes were integrated into an MEV construct with adjuvant and linkers, forming a fully immunogenic vaccine candidate. Comprehensive analyses encompassed the evaluation of immunological and physicochemical properties, determination of tertiary structure, molecular docking with Toll-Like Receptors (TLR), molecular dynamics (MD) simulations for all atoms, and immune simulations. Our MEV comprises 534 amino acids, featuring 6 cytotoxic T lymphocyte, 8 helper T lymphocyte, and 7 linear B lymphocyte epitopes, demonstrating high antigenicity and stability. Notably, molecular docking studies and triplicate MD simulations revealed enhanced interactions and stability of MEV with the TLR4 complex compared to TLR2. In addition, the immune simulation indicated the capacity to effectively induce elevated levels of antibodies and cytokines, emphasizing the vaccine's robust immunogenic response. This study presents a promising MEV against TB, exhibiting favorable immunological and physicochemical attributes. The findings provide theoretical support for TB vaccine development. Our study aligns with the global initiative of the End MTB Strategy, emphasizing its potential impact on addressing persistent challenges in TB control.http://www.sciencedirect.com/science/article/pii/S2405805X24000449Mycobacterium tuberculosisTuberculosisMultiepitope vaccineDocking molecularMolecular dynamics simulationImmune simulation |
| spellingShingle | Truc Ly Nguyen Heebal Kim Discovering peptides and computational investigations of a multiepitope vaccine target Mycobacterium tuberculosis Synthetic and Systems Biotechnology Mycobacterium tuberculosis Tuberculosis Multiepitope vaccine Docking molecular Molecular dynamics simulation Immune simulation |
| title | Discovering peptides and computational investigations of a multiepitope vaccine target Mycobacterium tuberculosis |
| title_full | Discovering peptides and computational investigations of a multiepitope vaccine target Mycobacterium tuberculosis |
| title_fullStr | Discovering peptides and computational investigations of a multiepitope vaccine target Mycobacterium tuberculosis |
| title_full_unstemmed | Discovering peptides and computational investigations of a multiepitope vaccine target Mycobacterium tuberculosis |
| title_short | Discovering peptides and computational investigations of a multiepitope vaccine target Mycobacterium tuberculosis |
| title_sort | discovering peptides and computational investigations of a multiepitope vaccine target mycobacterium tuberculosis |
| topic | Mycobacterium tuberculosis Tuberculosis Multiepitope vaccine Docking molecular Molecular dynamics simulation Immune simulation |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X24000449 |
| work_keys_str_mv | AT truclynguyen discoveringpeptidesandcomputationalinvestigationsofamultiepitopevaccinetargetmycobacteriumtuberculosis AT heebalkim discoveringpeptidesandcomputationalinvestigationsofamultiepitopevaccinetargetmycobacteriumtuberculosis |