Use of Soluble Extracellular Regions of MmpL (SERoM) as Vaccines for Tuberculosis

Abstract The current vaccine for tuberculosis (TB) is a live attenuated strain of Mycobacterium bovis (BCG) and while effective at reducing the potential for disseminated TB in young children its disease protection rates in adults is highly variable while it confers little protection against latent...

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Autores principales:	Emily J. Strong, Nicholas P. West
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/01e5b8b2db0b4b968747ff164106409d
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spelling	oai:doaj.org-article:01e5b8b2db0b4b968747ff164106409d2021-12-02T15:07:49ZUse of Soluble Extracellular Regions of MmpL (SERoM) as Vaccines for Tuberculosis10.1038/s41598-018-23893-32045-2322https://doaj.org/article/01e5b8b2db0b4b968747ff164106409d2018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-23893-3https://doaj.org/toc/2045-2322Abstract The current vaccine for tuberculosis (TB) is a live attenuated strain of Mycobacterium bovis (BCG) and while effective at reducing the potential for disseminated TB in young children its disease protection rates in adults is highly variable while it confers little protection against latent TB. With these limitations a new vaccine is desperately needed. We investigated the efficacy of three members of the mycobacterial membrane protein Large (MmpL) family as potential subunit vaccines for TB. MmpLs are large, multifunctional integral membrane proteins, and as such are recalcitrant to purification. Here, we describe a strategy of producing synthetic antigens comprised of the soluble, extracellular regions of MmpL (SERoM)-1, MmpL8 and MmpL10 (SERoM-8 and 10 respectively) as potential vaccine candidates. SERoM-1 and SERoM-8 were determined to be highly immunogenic by IFN-γ ELISpot assays, with 0.1% of all splenocytes from SERoM-1 vaccinated mice producing IFN-γ when re-stimulated with MmpL1. A combined SERoM-1, −8 and −10 vaccine demonstrated significant protection against M. tuberculosis challenge in a murine model of TB, resulting in approximately 10-fold reduction in bacterial numbers following challenge in both the lungs and spleens compared to adjuvant only vaccinated mice. These protective effects were comparable to that achieved with BCG.Emily J. StrongNicholas P. WestNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-7 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emily J. Strong Nicholas P. West Use of Soluble Extracellular Regions of MmpL (SERoM) as Vaccines for Tuberculosis
description	Abstract The current vaccine for tuberculosis (TB) is a live attenuated strain of Mycobacterium bovis (BCG) and while effective at reducing the potential for disseminated TB in young children its disease protection rates in adults is highly variable while it confers little protection against latent TB. With these limitations a new vaccine is desperately needed. We investigated the efficacy of three members of the mycobacterial membrane protein Large (MmpL) family as potential subunit vaccines for TB. MmpLs are large, multifunctional integral membrane proteins, and as such are recalcitrant to purification. Here, we describe a strategy of producing synthetic antigens comprised of the soluble, extracellular regions of MmpL (SERoM)-1, MmpL8 and MmpL10 (SERoM-8 and 10 respectively) as potential vaccine candidates. SERoM-1 and SERoM-8 were determined to be highly immunogenic by IFN-γ ELISpot assays, with 0.1% of all splenocytes from SERoM-1 vaccinated mice producing IFN-γ when re-stimulated with MmpL1. A combined SERoM-1, −8 and −10 vaccine demonstrated significant protection against M. tuberculosis challenge in a murine model of TB, resulting in approximately 10-fold reduction in bacterial numbers following challenge in both the lungs and spleens compared to adjuvant only vaccinated mice. These protective effects were comparable to that achieved with BCG.
format	article
author	Emily J. Strong Nicholas P. West
author_facet	Emily J. Strong Nicholas P. West
author_sort	Emily J. Strong
title	Use of Soluble Extracellular Regions of MmpL (SERoM) as Vaccines for Tuberculosis
title_short	Use of Soluble Extracellular Regions of MmpL (SERoM) as Vaccines for Tuberculosis
title_full	Use of Soluble Extracellular Regions of MmpL (SERoM) as Vaccines for Tuberculosis
title_fullStr	Use of Soluble Extracellular Regions of MmpL (SERoM) as Vaccines for Tuberculosis
title_full_unstemmed	Use of Soluble Extracellular Regions of MmpL (SERoM) as Vaccines for Tuberculosis
title_sort	use of soluble extracellular regions of mmpl (serom) as vaccines for tuberculosis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/01e5b8b2db0b4b968747ff164106409d
work_keys_str_mv	AT emilyjstrong useofsolubleextracellularregionsofmmplseromasvaccinesfortuberculosis AT nicholaspwest useofsolubleextracellularregionsofmmplseromasvaccinesfortuberculosis
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Use of Soluble Extracellular Regions of MmpL (SERoM) as Vaccines for Tuberculosis

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