Subunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models

Abstract The nontuberculous mycobacteria (NTM) Mycobacterium avium is a clinically significant pathogen that can cause a wide range of maladies, including tuberculosis-like pulmonary disease. An immunocompromised host status, either genetically or acutely acquired, presents a large risk for progress...

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Autores principales:	Sasha E. Larsen, Valerie A. Reese, Tiffany Pecor, Bryan J. Berube, Sarah K. Cooper, Guy Brewer, Diane Ordway, Marcela Henao-Tamayo, Brendan K. Podell, Susan L. Baldwin, Rhea N. Coler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/927dd0386d3f47ee8d7c92fa46bca032
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spelling	oai:doaj.org-article:927dd0386d3f47ee8d7c92fa46bca0322021-12-02T13:41:00ZSubunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models10.1038/s41598-021-88291-82045-2322https://doaj.org/article/927dd0386d3f47ee8d7c92fa46bca0322021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88291-8https://doaj.org/toc/2045-2322Abstract The nontuberculous mycobacteria (NTM) Mycobacterium avium is a clinically significant pathogen that can cause a wide range of maladies, including tuberculosis-like pulmonary disease. An immunocompromised host status, either genetically or acutely acquired, presents a large risk for progressive NTM infections. Due to this quietly emerging health threat, we evaluated the ability of a recombinant fusion protein ID91 combined with GLA-SE [glucopyranosyl lipid adjuvant, a toll like receptor 4 agonist formulated in an oil-in-water stable nano-emulsion] to confer protection in both C57BL/6 (wild type) and Beige (immunocompromised) mouse models. We optimized an aerosol challenge model using a clinical NTM isolate: M. avium 2-151 smt, observed bacterial growth kinetics, colony morphology, drug sensitivity and histopathology, characterized the influx of pulmonary immune cells, and confirmed the immunogenicity of ID91 in both mouse models. To determine prophylactic vaccine efficacy against this M. avium isolate, mice were immunized with either ID91 + GLA-SE or bacillus Calmette–Guérin (BCG). Immunocompromised Beige mice displayed a delayed influx of innate and adaptive immune cells resulting in a sustained and increased bacterial burden in the lungs and spleen compared to C57BL/6 mice. Importantly, both ID91 + GLA-SE and BCG vaccines significantly reduced pulmonary bacterial burden in both mouse strains. This work is a proof-of-concept study of subunit vaccine-induced protection against NTM.Sasha E. LarsenValerie A. ReeseTiffany PecorBryan J. BerubeSarah K. CooperGuy BrewerDiane OrdwayMarcela Henao-TamayoBrendan K. PodellSusan L. BaldwinRhea N. ColerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sasha E. Larsen Valerie A. Reese Tiffany Pecor Bryan J. Berube Sarah K. Cooper Guy Brewer Diane Ordway Marcela Henao-Tamayo Brendan K. Podell Susan L. Baldwin Rhea N. Coler Subunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models
description	Abstract The nontuberculous mycobacteria (NTM) Mycobacterium avium is a clinically significant pathogen that can cause a wide range of maladies, including tuberculosis-like pulmonary disease. An immunocompromised host status, either genetically or acutely acquired, presents a large risk for progressive NTM infections. Due to this quietly emerging health threat, we evaluated the ability of a recombinant fusion protein ID91 combined with GLA-SE [glucopyranosyl lipid adjuvant, a toll like receptor 4 agonist formulated in an oil-in-water stable nano-emulsion] to confer protection in both C57BL/6 (wild type) and Beige (immunocompromised) mouse models. We optimized an aerosol challenge model using a clinical NTM isolate: M. avium 2-151 smt, observed bacterial growth kinetics, colony morphology, drug sensitivity and histopathology, characterized the influx of pulmonary immune cells, and confirmed the immunogenicity of ID91 in both mouse models. To determine prophylactic vaccine efficacy against this M. avium isolate, mice were immunized with either ID91 + GLA-SE or bacillus Calmette–Guérin (BCG). Immunocompromised Beige mice displayed a delayed influx of innate and adaptive immune cells resulting in a sustained and increased bacterial burden in the lungs and spleen compared to C57BL/6 mice. Importantly, both ID91 + GLA-SE and BCG vaccines significantly reduced pulmonary bacterial burden in both mouse strains. This work is a proof-of-concept study of subunit vaccine-induced protection against NTM.
format	article
author	Sasha E. Larsen Valerie A. Reese Tiffany Pecor Bryan J. Berube Sarah K. Cooper Guy Brewer Diane Ordway Marcela Henao-Tamayo Brendan K. Podell Susan L. Baldwin Rhea N. Coler
author_facet	Sasha E. Larsen Valerie A. Reese Tiffany Pecor Bryan J. Berube Sarah K. Cooper Guy Brewer Diane Ordway Marcela Henao-Tamayo Brendan K. Podell Susan L. Baldwin Rhea N. Coler
author_sort	Sasha E. Larsen
title	Subunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models
title_short	Subunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models
title_full	Subunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models
title_fullStr	Subunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models
title_full_unstemmed	Subunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models
title_sort	subunit vaccine protects against a clinical isolate of mycobacterium avium in wild type and immunocompromised mouse models
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/927dd0386d3f47ee8d7c92fa46bca032
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Subunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models

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