Immunodominant Mycobacterium tuberculosis Protein Rv1507A Elicits Th1 Response and Modulates Host Macrophage Effector Functions

( ) persists as latent infection in nearly a quarter of the global population and remains the leading cause of death among infectious diseases. While BCG is the only vaccine for TB, its inability to provide complete protection makes it imperative to engineer BCG such that it expresses immunodominant...

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Published inFrontiers in immunology Vol. 11; p. 1199
Main Authors Arora, Simran Kaur, Alam, Anwar, Naqvi, Nilofer, Ahmad, Javeed, Sheikh, Javaid Ahmad, Rahman, Syed Asad, Hasnain, Seyed Ehtesham, Ehtesham, Nasreen Zafar
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 21.07.2020
Subjects
Animals
Antibodies, Bacterial - immunology
Antigens, Bacterial - immunology
CD4+/CD8+ T cells
central memory
effector memory
Humans
Immunodominant Epitopes
Immunology
Macrophages - immunology
Mice
Mycobacterium smegmatis knock-in
Mycobacterium tuberculosis - immunology
TB subunit vaccine
Th1 Cells - immunology
Tuberculosis - immunology
Tuberculosis Vaccines - immunology
CD4+/CD8+ T cells
TB subunit vaccine
Mycobacterium smegmatis knock-in
effector memory
central memory
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Abstract ( ) persists as latent infection in nearly a quarter of the global population and remains the leading cause of death among infectious diseases. While BCG is the only vaccine for TB, its inability to provide complete protection makes it imperative to engineer BCG such that it expresses immunodominant antigens that can enhance its protective potential. comparative genomic analysis of Mycobacterium species identified Rv1507A as a "signature protein" found exclusively in . (cell lines) and experiments carried out in mice, using purified recombinant Rv1507A revealed it to be a pro-inflammatory molecule, eliciting significantly high levels of IL-6, TNF-α, and IL-12. There was increased expression of activation markers CD69, CD80, CD86, antigen presentation molecules (MHC I/MHCII), and associated Th1 type of immune response. Rv1507A knocked-in also induced significantly higher pro-inflammatory Th1 response and higher survivability under stress conditions, both (macrophage RAW264.7 cells) and (mice). Sera derived from human TB patients showed significantly enhanced B-cell response against Rv1507A. The ability of Rv1507A to induce immuno-modulatory effect, B cell response, and significant memory response, renders it a putative vaccine candidate that demands further exploration.
AbstractList Mycobacterium tuberculosis (M. tb) persists as latent infection in nearly a quarter of the global population and remains the leading cause of death among infectious diseases. While BCG is the only vaccine for TB, its inability to provide complete protection makes it imperative to engineer BCG such that it expresses immunodominant antigens that can enhance its protective potential. In-silico comparative genomic analysis of Mycobacterium species identified M. tb Rv1507A as a “signature protein” found exclusively in M. tb. In-vitro (cell lines) and in-vivo experiments carried out in mice, using purified recombinant Rv1507A revealed it to be a pro-inflammatory molecule, eliciting significantly high levels of IL-6, TNF-α, and IL-12. There was increased expression of activation markers CD69, CD80, CD86, antigen presentation molecules (MHC I/MHCII), and associated Th1 type of immune response. Rv1507A knocked-in M. smegmatis also induced significantly higher pro-inflammatory Th1 response and higher survivability under stress conditions, both in-vitro (macrophage RAW264.7 cells) and in-vivo (mice). Sera derived from human TB patients showed significantly enhanced B-cell response against M. tb Rv1507A. The ability of M. tb Rv1507A to induce immuno-modulatory effect, B cell response, and significant memory response, renders it a putative vaccine candidate that demands further exploration.
Mycobacterium tuberculosis ( M. tb ) persists as latent infection in nearly a quarter of the global population and remains the leading cause of death among infectious diseases. While BCG is the only vaccine for TB, its inability to provide complete protection makes it imperative to engineer BCG such that it expresses immunodominant antigens that can enhance its protective potential. In-silico comparative genomic analysis of Mycobacterium species identified M. tb Rv1507A as a “signature protein” found exclusively in M. tb . In-vitro (cell lines) and in-vivo experiments carried out in mice, using purified recombinant Rv1507A revealed it to be a pro-inflammatory molecule, eliciting significantly high levels of IL-6, TNF-α, and IL-12. There was increased expression of activation markers CD69, CD80, CD86, antigen presentation molecules (MHC I/MHCII), and associated Th1 type of immune response. Rv1507A knocked-in M. smegmatis also induced significantly higher pro-inflammatory Th1 response and higher survivability under stress conditions, both in-vitro (macrophage RAW264.7 cells) and in-vivo (mice). Sera derived from human TB patients showed significantly enhanced B-cell response against M. tb Rv1507A. The ability of M. tb Rv1507A to induce immuno-modulatory effect, B cell response, and significant memory response, renders it a putative vaccine candidate that demands further exploration.
( ) persists as latent infection in nearly a quarter of the global population and remains the leading cause of death among infectious diseases. While BCG is the only vaccine for TB, its inability to provide complete protection makes it imperative to engineer BCG such that it expresses immunodominant antigens that can enhance its protective potential. comparative genomic analysis of Mycobacterium species identified Rv1507A as a "signature protein" found exclusively in . (cell lines) and experiments carried out in mice, using purified recombinant Rv1507A revealed it to be a pro-inflammatory molecule, eliciting significantly high levels of IL-6, TNF-α, and IL-12. There was increased expression of activation markers CD69, CD80, CD86, antigen presentation molecules (MHC I/MHCII), and associated Th1 type of immune response. Rv1507A knocked-in also induced significantly higher pro-inflammatory Th1 response and higher survivability under stress conditions, both (macrophage RAW264.7 cells) and (mice). Sera derived from human TB patients showed significantly enhanced B-cell response against Rv1507A. The ability of Rv1507A to induce immuno-modulatory effect, B cell response, and significant memory response, renders it a putative vaccine candidate that demands further exploration.
Mycobacterium tuberculosis (M. tb) persists as latent infection in nearly a quarter of the global population and remains the leading cause of death among infectious diseases. While BCG is the only vaccine for TB, its inability to provide complete protection makes it imperative to engineer BCG such that it expresses immunodominant antigens that can enhance its protective potential. In-silico comparative genomic analysis of Mycobacterium species identified M. tb Rv1507A as a "signature protein" found exclusively in M. tb. In-vitro (cell lines) and in-vivo experiments carried out in mice, using purified recombinant Rv1507A revealed it to be a pro-inflammatory molecule, eliciting significantly high levels of IL-6, TNF-α, and IL-12. There was increased expression of activation markers CD69, CD80, CD86, antigen presentation molecules (MHC I/MHCII), and associated Th1 type of immune response. Rv1507A knocked-in M. smegmatis also induced significantly higher pro-inflammatory Th1 response and higher survivability under stress conditions, both in-vitro (macrophage RAW264.7 cells) and in-vivo (mice). Sera derived from human TB patients showed significantly enhanced B-cell response against M. tb Rv1507A. The ability of M. tb Rv1507A to induce immuno-modulatory effect, B cell response, and significant memory response, renders it a putative vaccine candidate that demands further exploration.Mycobacterium tuberculosis (M. tb) persists as latent infection in nearly a quarter of the global population and remains the leading cause of death among infectious diseases. While BCG is the only vaccine for TB, its inability to provide complete protection makes it imperative to engineer BCG such that it expresses immunodominant antigens that can enhance its protective potential. In-silico comparative genomic analysis of Mycobacterium species identified M. tb Rv1507A as a "signature protein" found exclusively in M. tb. In-vitro (cell lines) and in-vivo experiments carried out in mice, using purified recombinant Rv1507A revealed it to be a pro-inflammatory molecule, eliciting significantly high levels of IL-6, TNF-α, and IL-12. There was increased expression of activation markers CD69, CD80, CD86, antigen presentation molecules (MHC I/MHCII), and associated Th1 type of immune response. Rv1507A knocked-in M. smegmatis also induced significantly higher pro-inflammatory Th1 response and higher survivability under stress conditions, both in-vitro (macrophage RAW264.7 cells) and in-vivo (mice). Sera derived from human TB patients showed significantly enhanced B-cell response against M. tb Rv1507A. The ability of M. tb Rv1507A to induce immuno-modulatory effect, B cell response, and significant memory response, renders it a putative vaccine candidate that demands further exploration.
Author Alam, Anwar
Arora, Simran Kaur
Sheikh, Javaid Ahmad
Rahman, Syed Asad
Ahmad, Javeed
Ehtesham, Nasreen Zafar
Naqvi, Nilofer
Hasnain, Seyed Ehtesham
AuthorAffiliation 1 Institute of Molecular Medicine, Jamia Hamdard , New Delhi , India
2 ICMR-National Institute of Pathology , New Delhi , India
4 BioInception Pvt. Ltd. , Chelmsford , United Kingdom
5 Dr. Reddy's Institute of Life Sciences , Hyderabad , India
3 Department of Biotechnology, Jamia Hamdard , New Delhi , India
AuthorAffiliation_xml – name: 5 Dr. Reddy's Institute of Life Sciences , Hyderabad , India
– name: 4 BioInception Pvt. Ltd. , Chelmsford , United Kingdom
– name: 1 Institute of Molecular Medicine, Jamia Hamdard , New Delhi , India
– name: 2 ICMR-National Institute of Pathology , New Delhi , India
– name: 3 Department of Biotechnology, Jamia Hamdard , New Delhi , India
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– sequence: 2
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  givenname: Nasreen Zafar
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Copyright Copyright © 2020 Arora, Alam, Naqvi, Ahmad, Sheikh, Rahman, Hasnain and Ehtesham.
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Keywords CD4+/CD8+ T cells
TB subunit vaccine
Mycobacterium smegmatis knock-in
effector memory
central memory
Language English
License Copyright © 2020 Arora, Alam, Naqvi, Ahmad, Sheikh, Rahman, Hasnain and Ehtesham.
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.
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This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology
Edited by: Mario Alberto Flores-Valdez, CONACYT Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Mexico
These authors have contributed equally to this work
Reviewed by: Maria E. Sarmiento, Universiti Sains Malaysia Health Campus, Malaysia; Arshad Khan, McGovern Medical School, University of Texas Health Science Center at Houston, United States
Present address: Javeed Ahmad, Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD, United States
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SSID ssj0000493335
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Snippet ( ) persists as latent infection in nearly a quarter of the global population and remains the leading cause of death among infectious diseases. While BCG is...
Mycobacterium tuberculosis (M. tb) persists as latent infection in nearly a quarter of the global population and remains the leading cause of death among...
Mycobacterium tuberculosis ( M. tb ) persists as latent infection in nearly a quarter of the global population and remains the leading cause of death among...
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StartPage 1199
SubjectTerms Animals
Antibodies, Bacterial - immunology
Antigens, Bacterial - immunology
CD4+/CD8+ T cells
central memory
effector memory
Humans
Immunodominant Epitopes
Immunology
Macrophages - immunology
Mice
Mycobacterium smegmatis knock-in
Mycobacterium tuberculosis - immunology
TB subunit vaccine
Th1 Cells - immunology
Tuberculosis - immunology
Tuberculosis Vaccines - immunology
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Title Immunodominant Mycobacterium tuberculosis Protein Rv1507A Elicits Th1 Response and Modulates Host Macrophage Effector Functions
URI https://www.ncbi.nlm.nih.gov/pubmed/32793184
https://www.proquest.com/docview/2434477828
https://pubmed.ncbi.nlm.nih.gov/PMC7385400
https://doaj.org/article/6f5c9277fe3245bbb6d2f3a2c563dfda
Volume 11
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