Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice

Abstract Mycobacterium avium subspecies paratuberculosis (MAP) causes chronic progressive granulomatous enteritis leading to diarrhoea, weight loss, and eventual death in ruminants. Commercially available vaccines provide only partial protection against MAP infection and can compromise the use of bo...

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Autores principales:	Sandeep K. Gupta, Natalie A. Parlane, Dongwen Luo, Bernd H. A. Rehm, Axel Heiser, Bryce M. Buddle, D. Neil Wedlock
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/81a42884569a48c8bc3f1e3aff5f5f43
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spelling	oai:doaj.org-article:81a42884569a48c8bc3f1e3aff5f5f432021-12-02T11:57:56ZSelf-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice10.1038/s41598-020-79407-72045-2322https://doaj.org/article/81a42884569a48c8bc3f1e3aff5f5f432020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79407-7https://doaj.org/toc/2045-2322Abstract Mycobacterium avium subspecies paratuberculosis (MAP) causes chronic progressive granulomatous enteritis leading to diarrhoea, weight loss, and eventual death in ruminants. Commercially available vaccines provide only partial protection against MAP infection and can compromise the use of bovine tuberculosis diagnostic tests. Here, we report the development of a protein-particle-based vaccine containing MAP antigens Ag85A202–347-SOD1–72-Ag85B173–330-74F1–148+669–786 as a fusion (‘MAP fusion protein particle’). The fusion antigen displayed on protein particles was identified using mass spectrometry. Surface exposure and accessibility of the fusion antigen was confirmed by flow cytometry and ELISA. The MAP fusion protein particle vaccine induced strong antigen-specific T-cell immune responses in mice, as indicated by increased cytokine (IFN-γ and IL-17A) and costimulatory signals (CD40 and CD86) in these animals. Following MAP-challenge, a significant reduction in bacterial burden was observed in multiple organs of the mice vaccinated with the MAP fusion protein particle vaccine compared with the PBS group. The reduction in severity of MAP infection conferred by the MAP fusion protein particle vaccine was similar to that of Silirum and recombinant protein vaccines. Overall, the results provide evidence that MAP antigens can be engineered as a protein particulate vaccine capable of inducing immunity against MAP infection. This utility offers an attractive platform for production of low-cost particulate vaccines against other intracellular pathogens.Sandeep K. GuptaNatalie A. ParlaneDongwen LuoBernd H. A. RehmAxel HeiserBryce M. BuddleD. Neil WedlockNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sandeep K. Gupta Natalie A. Parlane Dongwen Luo Bernd H. A. Rehm Axel Heiser Bryce M. Buddle D. Neil Wedlock Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice
description	Abstract Mycobacterium avium subspecies paratuberculosis (MAP) causes chronic progressive granulomatous enteritis leading to diarrhoea, weight loss, and eventual death in ruminants. Commercially available vaccines provide only partial protection against MAP infection and can compromise the use of bovine tuberculosis diagnostic tests. Here, we report the development of a protein-particle-based vaccine containing MAP antigens Ag85A202–347-SOD1–72-Ag85B173–330-74F1–148+669–786 as a fusion (‘MAP fusion protein particle’). The fusion antigen displayed on protein particles was identified using mass spectrometry. Surface exposure and accessibility of the fusion antigen was confirmed by flow cytometry and ELISA. The MAP fusion protein particle vaccine induced strong antigen-specific T-cell immune responses in mice, as indicated by increased cytokine (IFN-γ and IL-17A) and costimulatory signals (CD40 and CD86) in these animals. Following MAP-challenge, a significant reduction in bacterial burden was observed in multiple organs of the mice vaccinated with the MAP fusion protein particle vaccine compared with the PBS group. The reduction in severity of MAP infection conferred by the MAP fusion protein particle vaccine was similar to that of Silirum and recombinant protein vaccines. Overall, the results provide evidence that MAP antigens can be engineered as a protein particulate vaccine capable of inducing immunity against MAP infection. This utility offers an attractive platform for production of low-cost particulate vaccines against other intracellular pathogens.
format	article
author	Sandeep K. Gupta Natalie A. Parlane Dongwen Luo Bernd H. A. Rehm Axel Heiser Bryce M. Buddle D. Neil Wedlock
author_facet	Sandeep K. Gupta Natalie A. Parlane Dongwen Luo Bernd H. A. Rehm Axel Heiser Bryce M. Buddle D. Neil Wedlock
author_sort	Sandeep K. Gupta
title	Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice
title_short	Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice
title_full	Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice
title_fullStr	Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice
title_full_unstemmed	Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice
title_sort	self-assembled particulate vaccine elicits strong immune responses and reduces mycobacterium avium subsp. paratuberculosis infection in mice
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/81a42884569a48c8bc3f1e3aff5f5f43
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Self-assembled particulate vaccine elicits strong immune responses and reduces Mycobacterium avium subsp. paratuberculosis infection in mice

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