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Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model

BACKGROUND: Tuberculosis (TB) is still a global infectious disease that seriously threatens human beings. The only licensed TB vaccine Bacille Calmette-Guérin (BCG)’s protective efficacy varies significantly among populations and regions. It is very urgent to develop more effective vaccines. METHODS...

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Autores principales: Gong, Wenping, Liang, Yan, Mi, Jie, Jia, Zaixing, Xue, Yong, Wang, Jie, Wang, Lan, Zhou, Yusen, Sun, Shihui, Wu, Xueqiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108698/
https://www.ncbi.nlm.nih.gov/pubmed/33981313
http://dx.doi.org/10.3389/fimmu.2021.666290
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author Gong, Wenping
Liang, Yan
Mi, Jie
Jia, Zaixing
Xue, Yong
Wang, Jie
Wang, Lan
Zhou, Yusen
Sun, Shihui
Wu, Xueqiong
author_facet Gong, Wenping
Liang, Yan
Mi, Jie
Jia, Zaixing
Xue, Yong
Wang, Jie
Wang, Lan
Zhou, Yusen
Sun, Shihui
Wu, Xueqiong
author_sort Gong, Wenping
collection PubMed
description BACKGROUND: Tuberculosis (TB) is still a global infectious disease that seriously threatens human beings. The only licensed TB vaccine Bacille Calmette-Guérin (BCG)’s protective efficacy varies significantly among populations and regions. It is very urgent to develop more effective vaccines. METHODS: In this study, eleven candidate proteins of Mycobacterium tuberculosis were selected to predict peptides with high-affinity binding capacity for the HLA-DRB1*01:01 molecule. The immunodominant peptides were identified with the enzyme-linked immunospot assay (ELISPOT) and linked in silico to result in a novel polypeptide vaccine in Escherichia coli cells. The vaccine’s protective efficacy was evaluated in humanized and wild-type C57BL/6 mice. The potential immune protective mechanisms were explored with Enzyme-linked Immunosorbent Assay (ELISA), flow cytometry, and ELISPOT. RESULTS: Six immunodominant peptides screened from 50 predicted peptides were used to construct a new polypeptide vaccine named MP3RT. After challenge with M. tuberculosis, the colony-forming units (CFUs), lung lesion area, and the number of inflammatory cells in humanized mice rather than wild-type mice vaccinated with MP3RT were significantly lower than these in mice immunized with PBS. The humanized mice vaccinated with MP3RT revealed significant increases in IFN-γ cytokine production, IFN-γ(+) T lymphocytes, CD3(+)IFN-γ(+) T lymphocytes, and the MP3RT-specific IgG antibody. CONCLUSIONS: Taken together, MP3RT is a promising peptides-based TB vaccine characterized by inducing high levels of IFN-γ and CD3(+)IFN-γ(+) T lymphocytes in humanized mice. These new findings will lay a foundation for the development of peptides-based vaccines against TB.
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spelling pubmed-81086982021-05-11 Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model Gong, Wenping Liang, Yan Mi, Jie Jia, Zaixing Xue, Yong Wang, Jie Wang, Lan Zhou, Yusen Sun, Shihui Wu, Xueqiong Front Immunol Immunology BACKGROUND: Tuberculosis (TB) is still a global infectious disease that seriously threatens human beings. The only licensed TB vaccine Bacille Calmette-Guérin (BCG)’s protective efficacy varies significantly among populations and regions. It is very urgent to develop more effective vaccines. METHODS: In this study, eleven candidate proteins of Mycobacterium tuberculosis were selected to predict peptides with high-affinity binding capacity for the HLA-DRB1*01:01 molecule. The immunodominant peptides were identified with the enzyme-linked immunospot assay (ELISPOT) and linked in silico to result in a novel polypeptide vaccine in Escherichia coli cells. The vaccine’s protective efficacy was evaluated in humanized and wild-type C57BL/6 mice. The potential immune protective mechanisms were explored with Enzyme-linked Immunosorbent Assay (ELISA), flow cytometry, and ELISPOT. RESULTS: Six immunodominant peptides screened from 50 predicted peptides were used to construct a new polypeptide vaccine named MP3RT. After challenge with M. tuberculosis, the colony-forming units (CFUs), lung lesion area, and the number of inflammatory cells in humanized mice rather than wild-type mice vaccinated with MP3RT were significantly lower than these in mice immunized with PBS. The humanized mice vaccinated with MP3RT revealed significant increases in IFN-γ cytokine production, IFN-γ(+) T lymphocytes, CD3(+)IFN-γ(+) T lymphocytes, and the MP3RT-specific IgG antibody. CONCLUSIONS: Taken together, MP3RT is a promising peptides-based TB vaccine characterized by inducing high levels of IFN-γ and CD3(+)IFN-γ(+) T lymphocytes in humanized mice. These new findings will lay a foundation for the development of peptides-based vaccines against TB. Frontiers Media S.A. 2021-04-26 /pmc/articles/PMC8108698/ /pubmed/33981313 http://dx.doi.org/10.3389/fimmu.2021.666290 Text en Copyright © 2021 Gong, Liang, Mi, Jia, Xue, Wang, Wang, Zhou, Sun and Wu https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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.
spellingShingle Immunology
Gong, Wenping
Liang, Yan
Mi, Jie
Jia, Zaixing
Xue, Yong
Wang, Jie
Wang, Lan
Zhou, Yusen
Sun, Shihui
Wu, Xueqiong
Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model
title Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model
title_full Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model
title_fullStr Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model
title_full_unstemmed Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model
title_short Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model
title_sort peptides-based vaccine mp3rt induced protective immunity against mycobacterium tuberculosis infection in a humanized mouse model
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108698/
https://www.ncbi.nlm.nih.gov/pubmed/33981313
http://dx.doi.org/10.3389/fimmu.2021.666290
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