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Attenuated Salmonella Typhimurium expressing Salmonella Paratyphoid A O-antigen induces protective immune responses against two Salmonella strains.
Virulence ( IF 5.2 ) Pub Date : 2019-01-14 , DOI: 10.1080/21505594.2018.1559673
Qing Liu 1 , Pei Li 1 , Hongyan Luo 1 , Roy Curtiss 2 , Qingke Kong 1, 2
Affiliation  

Salmonella enterica serovar Paratyphi A is the main causative agent of paratyphoid fever in many Asian countries. As paratyphoid is spread by the fecal-oral route, the most effective means of controlling S. Paratyphi A infection is through the availability of clean water supplies and working sanitation services. Because sanitation facilities improve slowly in these poor areas and antibiotic resistance is severe, the development of a safe and effective vaccine remains a priority for controlling the spread of paratyphoid disease. In this study, we investigated the strategy of heterologous O-antigenic O2 serotype (S. Paratyphi A characterized) conversion in S. Typhimurium to prevent paratyphoid infections. A series of S. Typhimurium mutants were constructed with replacement of abe, wzxB1 and wbaVB1 genes with respective prt-tyvA1, wzxA1 and wbaVA1, and the results showed that only three genes including prt, wbaVA1 and wzxA1 from S. Paratyphi A presence enable S. Typhimurium to sufficiently express O2 antigen polysaccharide. We also constructed a series of live attenuated S. Typhimurium vaccine candidates expressing heterologous O2 O-antigens, and a mouse model was used to evaluate the immunogenicity of live vaccines. ELISA data showed that vaccine candidates could induce a comparatively high level of S. Paratyphi A and/or S. Typhimurium LPS-specific IgG and IgA responses in murine model, and IgG2a levels were consistently higher than IgG1 levels. Moreover, the functional properties of serum antibodies were evaluated using in vitro C3 complement deposition and opsonophagocytic assays. Our work highlights the potential for developing S. Typhimurium live vaccines against S. Paratyphi A.



中文翻译:

表达减毒副伤寒沙门氏菌A型O抗原的减毒鼠伤寒沙门氏菌诱导针对两种沙门氏菌菌株的保护性免疫应答。

在许多亚洲国家,肠炎沙门氏菌血清副伤寒A是副伤寒的主要病原。由于副伤寒是通过粪经途径传播的,因此是控制S的最有效手段。甲型副伤寒是通过提供干净的水和工作卫生服务来感染的。由于这些贫困地区的卫生设施进展缓慢,并且抗生素耐药性很强,因此,开发安全有效的疫苗仍然是控制副伤寒疾病传播的重点。在这项研究中,我们研究了异源O型抗原血清型O2(战略小号英寸甲型副伤寒特点)转换小号。鼠伤寒可预防副伤寒感染。S系列。鼠伤寒沙门氏菌突变体与替换构造安倍,WZX B1wbaV B1基因与相应PRT-tyv A1WZX A1wbaV A1,结果显示,只有三个基因包括PRT,wbaV A1WZX A1小号。副伤寒甲存在使小号。鼠伤寒充分表达O2抗原多糖。我们还构造了一系列的实时衰减S。表达异源O2 O抗原的鼠伤寒疫苗候选物,小鼠模型用于评估活疫苗的免疫原性。ELISA数据显示,候选疫苗可诱导的较高水平小号。副伤寒A和/或小号。鼠模型中鼠伤寒LPS特异的IgG和IgA反应以及IgG2a水平始终高于IgG1水平。此外,使用体外C3补体沉积和调理吞噬法评估了血清抗体的功能特性。我们的工作突出了开发S的潜力。鼠伤寒沙门氏菌对活疫苗小号。副伤寒A.

更新日期:2019-01-14
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