A DIVA vaccine strain lacking RpoS and the secondary messenger c-di-GMP for protection against salmonellosis in pigs
A DIVA vaccine strain lacking RpoS and the secondary messenger c-di-GMP for protection against salmonellosis in pigs
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DOI：
10.1186/s13567-019-0730-3
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发表时间：
2020-01-10
影响因子：
4.4
通讯作者：
Solano, Cristina
中科院分区：
文献类型：
--
作者：
Gil, Carmen;Latasa, Cristina;Solano, Cristina
沙门氏菌病是欧盟第二大常见的食源性人畜共患病，猪是这种病原体的主要宿主。猪生产中的沙门氏菌控制需要多种措施，其中疫苗接种可用于减少流行血清型（如沙门氏菌肠道血清型鼠伤寒沙门氏菌）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力和允许通过口服途径接种方面提供优势。然而，这些疫苗的主要失败是针对异源血清型实现的有限的交叉保护和对感染的血清学监测的干扰。我们最近表明，衰减的S。肠杆菌菌株（Delta XIII）对S.鼠感染模型中的鼠伤寒。Delta XIII菌株具有13个染色体缺失，使得其不能产生σ因子RpoS和合成环状-二-GMP（c-di-GMP）。在本研究中，我们的目的是测试Delta XIII毒株在猪中的保护作用，并研究Delta XIII的使用是否允许区分接种疫苗的猪和感染的猪。结果表明，用Delta XIII口服接种断奶前仔猪可交叉保护免受沙门氏菌的攻击。在断奶和屠宰时，通过减少粪便脱落和回盲部淋巴结定植来减少鼠伤寒沙门氏菌。接种猪在断奶时既未显示粪便散毒，也未显示疫苗株的组织持久性，确保屠宰时不存在Delta XIII株。此外，Delta XIII毒株中缺乏SEN4316蛋白，这使得能够开发血清学试验，该试验能够区分感染动物和接种动物（DIVA）。
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 (Delta XIII) is protective against S. Typhimurium in a murine infection model. Delta XIII 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 Delta XIII strain in swine and to investigate if the use of Delta XIII permits the discrimination of vaccinated from infected pigs. Results show that oral vaccination of pre-weaned piglets with Delta XIII 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 Delta XIII strain by the time of slaughter. Moreover, lack of the SEN4316 protein in Delta XIII strain allowed the development of a serological test that enabled the differentiation of infected from vaccinated animals (DIVA).