Recombinant attenuated Salmonella Typhimurium with heterologous expression of the Salmonella Choleraesuis O-polysaccharide: high immunogenicity and protection

Abstract Non-typhoidal Salmonella are associated with gastrointestinal disease worldwide and invasive disease in Africa. We constructed novel bivalent vaccines through the recombinant expression of heterologous O-antigens from Salmonella Choleraesuis in Salmonella Typhimurium. A recombinant Asd+ pla...

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Autores principales:	Xinxin Zhao, Qinlong Dai, Dekang Zhu, Mafeng Liu, Shun Chen, Kunfeng Sun, Qiao Yang, Ying Wu, Qingke Kong, Renyong Jia
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a9286ab7c4242bcbaefd653df4dc7a2
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spelling	oai:doaj.org-article:4a9286ab7c4242bcbaefd653df4dc7a22021-12-02T15:06:20ZRecombinant attenuated Salmonella Typhimurium with heterologous expression of the Salmonella Choleraesuis O-polysaccharide: high immunogenicity and protection10.1038/s41598-017-07689-52045-2322https://doaj.org/article/4a9286ab7c4242bcbaefd653df4dc7a22017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07689-5https://doaj.org/toc/2045-2322Abstract Non-typhoidal Salmonella are associated with gastrointestinal disease worldwide and invasive disease in Africa. We constructed novel bivalent vaccines through the recombinant expression of heterologous O-antigens from Salmonella Choleraesuis in Salmonella Typhimurium. A recombinant Asd+ plasmid pCZ1 with the cloned Salmonella Choleraesuis O-antigen gene cluster was introduced into three constructed Salmonella Typhimurium Δasd mutants: SLT11 (ΔrfbP), SLT12 (ΔrmlB-rfbP) and SLT16 (ΔrfbP ∆pagL::TT araCPBAD rfbP). Immunoblotting demonstrated that SLT11 (pCZ1) and SLT12 (pCZ1) efficiently expressed the heterologous O-antigen. In the presence of arabinose, SLT16 (pCZ1) expressed both the homologous and heterologous O-antigens, whereas in the absence of arabinose, SLT16 (pCZ1) mainly expressed the heterologous O-antigen. We deleted the crp/cya genes in SLT12 (pCZ1) and SLT16 (pCZ1) for attenuation purposes, generating the recombinant vaccine strains SLT17 (pCZ1) and SLT18 (pCZ1). Immunization with either SLT17 (pCZ1) or SLT18 (pCZ1) induced specific IgG against the heterologous O-antigen, which mediated significant killing of Salmonella Choleraesuis and provided full protection against a lethal homologous challenge in mice. Furthermore, SLT17 (pCZ1) or SLT18 (pCZ1) immunization resulted in 83% or 50% heterologous protection against Salmonella Choleraesuis challenge, respectively. Our study demonstrates that heterologous O-antigen expression is a promising strategy for the development of multivalent Salmonella vaccines.Xinxin ZhaoQinlong DaiDekang ZhuMafeng LiuShun ChenKunfeng SunQiao YangYing WuQingke KongRenyong JiaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xinxin Zhao Qinlong Dai Dekang Zhu Mafeng Liu Shun Chen Kunfeng Sun Qiao Yang Ying Wu Qingke Kong Renyong Jia Recombinant attenuated Salmonella Typhimurium with heterologous expression of the Salmonella Choleraesuis O-polysaccharide: high immunogenicity and protection
description	Abstract Non-typhoidal Salmonella are associated with gastrointestinal disease worldwide and invasive disease in Africa. We constructed novel bivalent vaccines through the recombinant expression of heterologous O-antigens from Salmonella Choleraesuis in Salmonella Typhimurium. A recombinant Asd+ plasmid pCZ1 with the cloned Salmonella Choleraesuis O-antigen gene cluster was introduced into three constructed Salmonella Typhimurium Δasd mutants: SLT11 (ΔrfbP), SLT12 (ΔrmlB-rfbP) and SLT16 (ΔrfbP ∆pagL::TT araCPBAD rfbP). Immunoblotting demonstrated that SLT11 (pCZ1) and SLT12 (pCZ1) efficiently expressed the heterologous O-antigen. In the presence of arabinose, SLT16 (pCZ1) expressed both the homologous and heterologous O-antigens, whereas in the absence of arabinose, SLT16 (pCZ1) mainly expressed the heterologous O-antigen. We deleted the crp/cya genes in SLT12 (pCZ1) and SLT16 (pCZ1) for attenuation purposes, generating the recombinant vaccine strains SLT17 (pCZ1) and SLT18 (pCZ1). Immunization with either SLT17 (pCZ1) or SLT18 (pCZ1) induced specific IgG against the heterologous O-antigen, which mediated significant killing of Salmonella Choleraesuis and provided full protection against a lethal homologous challenge in mice. Furthermore, SLT17 (pCZ1) or SLT18 (pCZ1) immunization resulted in 83% or 50% heterologous protection against Salmonella Choleraesuis challenge, respectively. Our study demonstrates that heterologous O-antigen expression is a promising strategy for the development of multivalent Salmonella vaccines.
format	article
author	Xinxin Zhao Qinlong Dai Dekang Zhu Mafeng Liu Shun Chen Kunfeng Sun Qiao Yang Ying Wu Qingke Kong Renyong Jia
author_facet	Xinxin Zhao Qinlong Dai Dekang Zhu Mafeng Liu Shun Chen Kunfeng Sun Qiao Yang Ying Wu Qingke Kong Renyong Jia
author_sort	Xinxin Zhao
title	Recombinant attenuated Salmonella Typhimurium with heterologous expression of the Salmonella Choleraesuis O-polysaccharide: high immunogenicity and protection
title_short	Recombinant attenuated Salmonella Typhimurium with heterologous expression of the Salmonella Choleraesuis O-polysaccharide: high immunogenicity and protection
title_full	Recombinant attenuated Salmonella Typhimurium with heterologous expression of the Salmonella Choleraesuis O-polysaccharide: high immunogenicity and protection
title_fullStr	Recombinant attenuated Salmonella Typhimurium with heterologous expression of the Salmonella Choleraesuis O-polysaccharide: high immunogenicity and protection
title_full_unstemmed	Recombinant attenuated Salmonella Typhimurium with heterologous expression of the Salmonella Choleraesuis O-polysaccharide: high immunogenicity and protection
title_sort	recombinant attenuated salmonella typhimurium with heterologous expression of the salmonella choleraesuis o-polysaccharide: high immunogenicity and protection
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4a9286ab7c4242bcbaefd653df4dc7a2
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Recombinant attenuated Salmonella Typhimurium with heterologous expression of the Salmonella Choleraesuis O-polysaccharide: high immunogenicity and protection

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