A bivalent protein r-PB, comprising PA and BclA immunodominant regions for comprehensive protection against Bacillus anthracis

Abstract Anthrax infection is primarily initiated by B. anthracis endospores that on entry into the host germinate to vegetative cells and cause severe bacteremia and toxaemia employing an array of host colonisation factors and the lethal tripartite toxin. The protective efficacy of conventional pro...

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Autores principales:	Saugata Majumder, Shreya Das, Vikas Somani, Shivakiran S. Makam, Kingston J. Joseph, Rakesh Bhatnagar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/896d0f5d25b8450da4ce012025b765a5
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spelling	oai:doaj.org-article:896d0f5d25b8450da4ce012025b765a52021-12-02T11:40:26ZA bivalent protein r-PB, comprising PA and BclA immunodominant regions for comprehensive protection against Bacillus anthracis10.1038/s41598-018-25502-92045-2322https://doaj.org/article/896d0f5d25b8450da4ce012025b765a52018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25502-9https://doaj.org/toc/2045-2322Abstract Anthrax infection is primarily initiated by B. anthracis endospores that on entry into the host germinate to vegetative cells and cause severe bacteremia and toxaemia employing an array of host colonisation factors and the lethal tripartite toxin. The protective efficacy of conventional protective antigen (PA) based anthrax vaccines is improved by co-administration with inactivated spores or its components. In the present study, using structural vaccinology rationale we synthesized a bivalent protein r-PB encompassing toxin (PAIV) and spore components (BclACTD) and characterized its protective efficacy against B. anthracis infection. Active immunization of mice with r-PB generated high titer circulating antibodies which facilitated the phagocytic uptake of spores, inhibited their germination to vegetative cells and completely neutralized anthrax toxins in vivo resulting in 100 % survival against anthrax toxin challenge. Proliferation of CD4+ T cell subsets with up-regulation of Th1 (IFN-γ, IL-2, and IL-12), Th2 (IL-5, IL-10) cytokines and balanced expression of IgG1:IgG2a antibody isotypes indicated the stimulation of both Th1 and Th2 subsets. The immunized mice exhibited 100 % survival upon challenge with B. anthracis spores or toxin indicating the ability of r-PB to provide comprehensive protection against anthrax. Our results thus demonstrate r-PB an efficient vaccine candidate against anthrax infection.Saugata MajumderShreya DasVikas SomaniShivakiran S. MakamKingston J. JosephRakesh BhatnagarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Saugata Majumder Shreya Das Vikas Somani Shivakiran S. Makam Kingston J. Joseph Rakesh Bhatnagar A bivalent protein r-PB, comprising PA and BclA immunodominant regions for comprehensive protection against Bacillus anthracis
description	Abstract Anthrax infection is primarily initiated by B. anthracis endospores that on entry into the host germinate to vegetative cells and cause severe bacteremia and toxaemia employing an array of host colonisation factors and the lethal tripartite toxin. The protective efficacy of conventional protective antigen (PA) based anthrax vaccines is improved by co-administration with inactivated spores or its components. In the present study, using structural vaccinology rationale we synthesized a bivalent protein r-PB encompassing toxin (PAIV) and spore components (BclACTD) and characterized its protective efficacy against B. anthracis infection. Active immunization of mice with r-PB generated high titer circulating antibodies which facilitated the phagocytic uptake of spores, inhibited their germination to vegetative cells and completely neutralized anthrax toxins in vivo resulting in 100 % survival against anthrax toxin challenge. Proliferation of CD4+ T cell subsets with up-regulation of Th1 (IFN-γ, IL-2, and IL-12), Th2 (IL-5, IL-10) cytokines and balanced expression of IgG1:IgG2a antibody isotypes indicated the stimulation of both Th1 and Th2 subsets. The immunized mice exhibited 100 % survival upon challenge with B. anthracis spores or toxin indicating the ability of r-PB to provide comprehensive protection against anthrax. Our results thus demonstrate r-PB an efficient vaccine candidate against anthrax infection.
format	article
author	Saugata Majumder Shreya Das Vikas Somani Shivakiran S. Makam Kingston J. Joseph Rakesh Bhatnagar
author_facet	Saugata Majumder Shreya Das Vikas Somani Shivakiran S. Makam Kingston J. Joseph Rakesh Bhatnagar
author_sort	Saugata Majumder
title	A bivalent protein r-PB, comprising PA and BclA immunodominant regions for comprehensive protection against Bacillus anthracis
title_short	A bivalent protein r-PB, comprising PA and BclA immunodominant regions for comprehensive protection against Bacillus anthracis
title_full	A bivalent protein r-PB, comprising PA and BclA immunodominant regions for comprehensive protection against Bacillus anthracis
title_fullStr	A bivalent protein r-PB, comprising PA and BclA immunodominant regions for comprehensive protection against Bacillus anthracis
title_full_unstemmed	A bivalent protein r-PB, comprising PA and BclA immunodominant regions for comprehensive protection against Bacillus anthracis
title_sort	bivalent protein r-pb, comprising pa and bcla immunodominant regions for comprehensive protection against bacillus anthracis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/896d0f5d25b8450da4ce012025b765a5
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A bivalent protein r-PB, comprising PA and BclA immunodominant regions for comprehensive protection against Bacillus anthracis

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