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A DIVA vaccine strain lacking RpoS and the secondary messenger c-di-GMP for protection against salmonellosis in pigs.
Veterinary Research ( IF 3.7 ) Pub Date : 2020-01-10 , DOI: 10.1186/s13567-019-0730-3
Carmen Gil 1 , Cristina Latasa 2 , Enrique García-Ona 1 , Isidro Lázaro 3 , Javier Labairu 3 , Maite Echeverz 1 , Saioa Burgui 1 , Begoña García 1 , Iñigo Lasa 1 , Cristina Solano 1
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Salmonellosis is the second most common food-borne zoonosis in the European Union, with pigs being a major reservoir of this pathogen. Salmonella control in pig production requires multiple measures amongst which vaccination may be used to reduce subclinical carriage and shedding of prevalent serovars, such as Salmonella enterica serovar Typhimurium. Live attenuated vaccine strains offer advantages in terms of enhancing cell mediated immunity and allowing inoculation by the oral route. However, main failures of these vaccines are the limited cross-protection achieved against heterologous serovars and interference with serological monitoring for infection. We have recently shown that an attenuated S. Enteritidis strain (ΔXIII) is protective against S. Typhimurium in a murine infection model. ΔXIII strain harbours 13 chromosomal deletions that make it unable to produce the sigma factor RpoS and synthesize cyclic-di-GMP (c-di-GMP). In this study, our objectives were to test the protective effects of ΔXIII strain in swine and to investigate if the use of ΔXIII permits the discrimination of vaccinated from infected pigs. Results show that oral vaccination of pre-weaned piglets with ΔXIII cross-protected against a challenge with S. Typhimurium by reducing faecal shedding and ileocaecal lymph nodes colonization, both at the time of weaning and slaughter. Vaccinated pigs showed neither faecal shedding nor tissue persistence of the vaccine strain at weaning, ensuring the absence of ΔXIII strain by the time of slaughter. Moreover, lack of the SEN4316 protein in ΔXIII strain allowed the development of a serological test that enabled the differentiation of infected from vaccinated animals (DIVA).

中文翻译:


缺乏 RpoS 和第二信使 c-di-GMP 的 DIVA 疫苗株,用于预防猪沙门氏菌病。



沙门氏菌病是欧盟第二常见的食源性人畜共患病,猪是这种病原体的主要宿主。养猪生产中的沙门氏菌控制需要采取多种措施,其中可以使用疫苗接种来减少流行血清型(例如鼠伤寒沙门氏菌)的亚临床携带和脱落。减毒活疫苗株在增强细胞介导的免疫和允许通过口服途径接种方面具有优势。然而,这些疫苗的主要失败之处在于针对异源血清型的交叉保护有限,并且干扰了感染的血清学监测。我们最近证明,在小鼠感染模型中,肠炎沙门氏菌减毒株(ΔXIII)对鼠伤寒沙门氏菌具有保护作用。 ΔXIII菌株具有13条染色体缺失,使其无法产生西格玛因子RpoS并合成环二GMP(c-di-GMP)。在这项研究中,我们的目标是测试 ΔXIII 菌株对猪的保护作用,并调查使用 ΔXIII 是否可以区分接种疫苗的猪和受感染的猪。结果表明,断奶前仔猪口服接种 ΔXIII 可通过减少断奶时和屠宰时的粪便排出和回盲部淋巴结定植,交叉保护其免受鼠伤寒沙门氏菌的攻击。接种疫苗的猪在断奶时既没有表现出粪便脱落,也没有表现出疫苗株的组织持久性,确保了屠宰时不存在 ΔXIII 株。此外,ΔXIII 菌株中缺乏 SEN4316 蛋白,因此可以开发血清学测试,从而区分感染动物和接种疫苗的动物 (DIVA)。
更新日期:2020-04-22
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