Mucosal vaccination with pili from Group A Streptococcus expressed on Lactococcus lactis generates protective immune responses

Abstract The human pathogen Group A Streptococcus (GAS) produces pili that are involved in adhesion and colonisation of the host. These surface-exposed pili are immunogenic and therefore represent an attractive target for vaccine development. The pilus is encoded in the genomic region known as the f...

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Autores principales:	Jacelyn M. S. Loh, Natalie Lorenz, Catherine J.-Y. Tsai, Adrina Hema J. Khemlani, Thomas Proft
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/efa58e577bca4160909851cb9564e2f3
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spelling	oai:doaj.org-article:efa58e577bca4160909851cb9564e2f32021-12-02T15:05:31ZMucosal vaccination with pili from Group A Streptococcus expressed on Lactococcus lactis generates protective immune responses10.1038/s41598-017-07602-02045-2322https://doaj.org/article/efa58e577bca4160909851cb9564e2f32017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07602-0https://doaj.org/toc/2045-2322Abstract The human pathogen Group A Streptococcus (GAS) produces pili that are involved in adhesion and colonisation of the host. These surface-exposed pili are immunogenic and therefore represent an attractive target for vaccine development. The pilus is encoded in the genomic region known as the fibronectin-collagen-T-antigen (FCT)-region, of which at least nine different types have been identified. In this study we investigate expressing two of the most common FCT-types (FCT-3 and FCT-4) in the food-grade bacteria Lactococcus lactis for use as a mucosal vaccine. We show that mucosally delivered L. lactis expressing GAS pili generates specific antibody responses in rabbits. Rabbit anti-pilus antibodies were shown to have both a neutralising effect on bacterial adhesion, and immunised rabbit antiserum was able to facilitate immune-mediated killing of bacteria via opsonophagocytosis. Furthermore, intranasal immunisation of mice improved clearance rates of GAS after nasopharyngeal challenge. These results demonstrate the potential for a novel, pilus-based vaccine to protect against GAS infections.Jacelyn M. S. LohNatalie LorenzCatherine J.-Y. TsaiAdrina Hema J. KhemlaniThomas ProftNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jacelyn M. S. Loh Natalie Lorenz Catherine J.-Y. Tsai Adrina Hema J. Khemlani Thomas Proft Mucosal vaccination with pili from Group A Streptococcus expressed on Lactococcus lactis generates protective immune responses
description	Abstract The human pathogen Group A Streptococcus (GAS) produces pili that are involved in adhesion and colonisation of the host. These surface-exposed pili are immunogenic and therefore represent an attractive target for vaccine development. The pilus is encoded in the genomic region known as the fibronectin-collagen-T-antigen (FCT)-region, of which at least nine different types have been identified. In this study we investigate expressing two of the most common FCT-types (FCT-3 and FCT-4) in the food-grade bacteria Lactococcus lactis for use as a mucosal vaccine. We show that mucosally delivered L. lactis expressing GAS pili generates specific antibody responses in rabbits. Rabbit anti-pilus antibodies were shown to have both a neutralising effect on bacterial adhesion, and immunised rabbit antiserum was able to facilitate immune-mediated killing of bacteria via opsonophagocytosis. Furthermore, intranasal immunisation of mice improved clearance rates of GAS after nasopharyngeal challenge. These results demonstrate the potential for a novel, pilus-based vaccine to protect against GAS infections.
format	article
author	Jacelyn M. S. Loh Natalie Lorenz Catherine J.-Y. Tsai Adrina Hema J. Khemlani Thomas Proft
author_facet	Jacelyn M. S. Loh Natalie Lorenz Catherine J.-Y. Tsai Adrina Hema J. Khemlani Thomas Proft
author_sort	Jacelyn M. S. Loh
title	Mucosal vaccination with pili from Group A Streptococcus expressed on Lactococcus lactis generates protective immune responses
title_short	Mucosal vaccination with pili from Group A Streptococcus expressed on Lactococcus lactis generates protective immune responses
title_full	Mucosal vaccination with pili from Group A Streptococcus expressed on Lactococcus lactis generates protective immune responses
title_fullStr	Mucosal vaccination with pili from Group A Streptococcus expressed on Lactococcus lactis generates protective immune responses
title_full_unstemmed	Mucosal vaccination with pili from Group A Streptococcus expressed on Lactococcus lactis generates protective immune responses
title_sort	mucosal vaccination with pili from group a streptococcus expressed on lactococcus lactis generates protective immune responses
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/efa58e577bca4160909851cb9564e2f3
work_keys_str_mv	AT jacelynmsloh mucosalvaccinationwithpilifromgroupastreptococcusexpressedonlactococcuslactisgeneratesprotectiveimmuneresponses AT natalielorenz mucosalvaccinationwithpilifromgroupastreptococcusexpressedonlactococcuslactisgeneratesprotectiveimmuneresponses AT catherinejytsai mucosalvaccinationwithpilifromgroupastreptococcusexpressedonlactococcuslactisgeneratesprotectiveimmuneresponses AT adrinahemajkhemlani mucosalvaccinationwithpilifromgroupastreptococcusexpressedonlactococcuslactisgeneratesprotectiveimmuneresponses AT thomasproft mucosalvaccinationwithpilifromgroupastreptococcusexpressedonlactococcuslactisgeneratesprotectiveimmuneresponses
_version_	1718388803313336320

Mucosal vaccination with pili from Group A Streptococcus expressed on Lactococcus lactis generates protective immune responses

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