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携带有猪霍乱沙门氏菌 O 多糖异源表达的重组减毒鼠伤寒沙门氏菌:高免疫原性和保护作用。

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

机构信息

Research Center of Avian Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, Sichuan, 611130, P.R. China.

Key Laboratory of Animal Disease and Human Health of Sichuan Province, Wenjiang, Chengdu, Sichuan, 611130, P.R. China.

出版信息

Sci Rep. 2017 Jul 28;7(1):7127. doi: 10.1038/s41598-017-07689-5.

DOI:10.1038/s41598-017-07689-5
PMID:28754982
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5533773/
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 araCP 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.

摘要

非伤寒沙门氏菌与全世界的胃肠道疾病和非洲的侵袭性疾病有关。我们通过在鼠伤寒沙门氏菌中重组表达猪霍乱沙门氏菌的异源 O 抗原,构建了新型双价疫苗。带有克隆的猪霍乱沙门氏菌 O 抗原基因簇的重组 Asd 质粒 pCZ1 被引入到三个构建的鼠伤寒沙门氏菌Δasd 突变株中:SLT11(ΔrfbP)、SLT12(ΔrmlB-rfbP)和 SLT16(ΔrfbPΔpagL::TT araCP rfbP)。免疫印迹表明,SLT11(pCZ1)和 SLT12(pCZ1)有效地表达了异源 O 抗原。在阿拉伯糖存在的情况下,SLT16(pCZ1)表达同源和异源 O 抗原,而在没有阿拉伯糖的情况下,SLT16(pCZ1)主要表达异源 O 抗原。我们为了减毒的目的在 SLT12(pCZ1)和 SLT16(pCZ1)中删除了 crp/cya 基因,产生了重组疫苗株 SLT17(pCZ1)和 SLT18(pCZ1)。用 SLT17(pCZ1)或 SLT18(pCZ1)免疫诱导了针对异源 O 抗原的特异性 IgG,该抗体介导了对猪霍乱沙门氏菌的显著杀伤,并在小鼠中提供了针对同源致命挑战的完全保护。此外,SLT17(pCZ1)或 SLT18(pCZ1)免疫分别导致对猪霍乱沙门氏菌攻击的 83%或 50%异源保护。我们的研究表明,异源 O 抗原表达是开发多价沙门氏菌疫苗的有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/46648bc9b114/41598_2017_7689_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/12c194b4624a/41598_2017_7689_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/32722922a064/41598_2017_7689_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/0c86c49e33e8/41598_2017_7689_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/a8dfcbf2389a/41598_2017_7689_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/fb2fad324ed7/41598_2017_7689_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/46648bc9b114/41598_2017_7689_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/12c194b4624a/41598_2017_7689_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/32722922a064/41598_2017_7689_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/0c86c49e33e8/41598_2017_7689_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/a8dfcbf2389a/41598_2017_7689_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/fb2fad324ed7/41598_2017_7689_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/5533773/46648bc9b114/41598_2017_7689_Fig6_HTML.jpg

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