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Particulate Mycobacterial Vaccines Induce Protective Immunity against Tuberculosis in Mice

Currently available vaccines fail to provide consistent protection against tuberculosis (TB). New, improved vaccines are urgently needed for controlling the disease. The mycobacterial antigen fusions H4 (Ag85B-TB10.4) and H28 (Ag85B-TB10.4-Rv2660c) have been shown to be very immunogenic and have bee...

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Autores principales: Chen, Shuxiong, Quan, Diana H., Wang, Xiaonan T., Sandford, Sarah, Kirman, Joanna R., Britton, Warwick J., Rehm, Bernd H. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402087/
https://www.ncbi.nlm.nih.gov/pubmed/34443891
http://dx.doi.org/10.3390/nano11082060
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author Chen, Shuxiong
Quan, Diana H.
Wang, Xiaonan T.
Sandford, Sarah
Kirman, Joanna R.
Britton, Warwick J.
Rehm, Bernd H. A.
author_facet Chen, Shuxiong
Quan, Diana H.
Wang, Xiaonan T.
Sandford, Sarah
Kirman, Joanna R.
Britton, Warwick J.
Rehm, Bernd H. A.
author_sort Chen, Shuxiong
collection PubMed
description Currently available vaccines fail to provide consistent protection against tuberculosis (TB). New, improved vaccines are urgently needed for controlling the disease. The mycobacterial antigen fusions H4 (Ag85B-TB10.4) and H28 (Ag85B-TB10.4-Rv2660c) have been shown to be very immunogenic and have been considered as potential candidates for TB vaccine development. However, soluble protein vaccines are often poorly immunogenic, but augmented immune responses can be induced when selected antigens are delivered in particulate form. This study investigated whether the mycobacterial antigen fusions H4 and H28 can induce protective immunity when assembled into particulate vaccines (polyester nanoparticle-H4, polyester nanoparticle-H28, H4 nanoparticles and H28 nanoparticles). The particulate mycobacterial vaccines were assembled inside an engineered endotoxin-free production strain of Escherichia coli at high yield. Vaccine nanoparticles were purified and induced long-lasting antigen-specific T cell responses and protective immunity in mice challenged by aerosol with virulent Mycobacterium tuberculosis. A significant reduction of M. tuberculosis CFU, up to 0.7-log(10) protection, occurred in the lungs of mice immunized with particulate vaccines in comparison to placebo-vaccinated mice (p < 0.0001). Polyester nanoparticles displaying the mycobacterial antigen fusion H4 induced a similar level of protective immunity in the lung when compared to M. bovis bacillus Calmette-Guérin (BCG), the currently approved TB vaccine. The safe and immunogenic polyester nanoparticle-H4 vaccine is a promising subunit vaccine candidate, as it can be cost-effectively manufactured and efficiently induces protection against TB.
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spelling pubmed-84020872021-08-29 Particulate Mycobacterial Vaccines Induce Protective Immunity against Tuberculosis in Mice Chen, Shuxiong Quan, Diana H. Wang, Xiaonan T. Sandford, Sarah Kirman, Joanna R. Britton, Warwick J. Rehm, Bernd H. A. Nanomaterials (Basel) Article Currently available vaccines fail to provide consistent protection against tuberculosis (TB). New, improved vaccines are urgently needed for controlling the disease. The mycobacterial antigen fusions H4 (Ag85B-TB10.4) and H28 (Ag85B-TB10.4-Rv2660c) have been shown to be very immunogenic and have been considered as potential candidates for TB vaccine development. However, soluble protein vaccines are often poorly immunogenic, but augmented immune responses can be induced when selected antigens are delivered in particulate form. This study investigated whether the mycobacterial antigen fusions H4 and H28 can induce protective immunity when assembled into particulate vaccines (polyester nanoparticle-H4, polyester nanoparticle-H28, H4 nanoparticles and H28 nanoparticles). The particulate mycobacterial vaccines were assembled inside an engineered endotoxin-free production strain of Escherichia coli at high yield. Vaccine nanoparticles were purified and induced long-lasting antigen-specific T cell responses and protective immunity in mice challenged by aerosol with virulent Mycobacterium tuberculosis. A significant reduction of M. tuberculosis CFU, up to 0.7-log(10) protection, occurred in the lungs of mice immunized with particulate vaccines in comparison to placebo-vaccinated mice (p < 0.0001). Polyester nanoparticles displaying the mycobacterial antigen fusion H4 induced a similar level of protective immunity in the lung when compared to M. bovis bacillus Calmette-Guérin (BCG), the currently approved TB vaccine. The safe and immunogenic polyester nanoparticle-H4 vaccine is a promising subunit vaccine candidate, as it can be cost-effectively manufactured and efficiently induces protection against TB. MDPI 2021-08-13 /pmc/articles/PMC8402087/ /pubmed/34443891 http://dx.doi.org/10.3390/nano11082060 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Shuxiong
Quan, Diana H.
Wang, Xiaonan T.
Sandford, Sarah
Kirman, Joanna R.
Britton, Warwick J.
Rehm, Bernd H. A.
Particulate Mycobacterial Vaccines Induce Protective Immunity against Tuberculosis in Mice
title Particulate Mycobacterial Vaccines Induce Protective Immunity against Tuberculosis in Mice
title_full Particulate Mycobacterial Vaccines Induce Protective Immunity against Tuberculosis in Mice
title_fullStr Particulate Mycobacterial Vaccines Induce Protective Immunity against Tuberculosis in Mice
title_full_unstemmed Particulate Mycobacterial Vaccines Induce Protective Immunity against Tuberculosis in Mice
title_short Particulate Mycobacterial Vaccines Induce Protective Immunity against Tuberculosis in Mice
title_sort particulate mycobacterial vaccines induce protective immunity against tuberculosis in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402087/
https://www.ncbi.nlm.nih.gov/pubmed/34443891
http://dx.doi.org/10.3390/nano11082060
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