Salmonella Typhimurium lacking the Znuabc transporter is attenuated and immunogenic in pigs.

Salmonella Typhimurium lacking the Znuabc transporter is attenuated and immunogenic in pigs.
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缺乏 Znuabc 转运蛋白的鼠伤寒沙门氏菌在猪体内是减毒的且具有免疫原性。

DOI:
10.1016/j.vaccine.2013.04.032
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发表时间:
2013
期刊:
影响因子:
5.5
通讯作者:
Alborali,GL
Alborali,GL
中科院分区:
医学3区
文献类型:
--
作者:
Pesciaroli,M;Gradassi,M;Martinelli,N;Ruggeri,J;Pistoia,C;Raffatellu,M;Magistrali,CF;Battistoni,A;Pasquali,P;Alborali,GL

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沙门氏菌污染的肉类正在成为工业化国家人类肠道感染的主要原因。减少人间沙门氏菌病病例的努力包括收获前和收获后的干预措施。在这种情况下,猪的疫苗接种可能是通过食物链消除/减少沙门氏菌负担的有效手段。我们之前已经证明缺乏ZnuABC转运体的鼠伤寒沙门菌(S. Typhimurium ΔznuABC)是一种很有希望的鼠伤寒沙门菌感染小鼠模型的候选活疫苗。在这项研究中,我们在猪身上证实了鼠伤寒沙门氏菌ΔznuABC的衰减。此外,我们还评估了鼠伤寒沙门氏菌ΔznuABC经口服给药给猪的安全性和免疫原性。我们监测了动物的临床状况,并对猪的粪便和血液样本分别进行了微生物培养和体液和细胞免疫反应的量化。接种减毒鼠伤寒沙门氏菌ΔznuABC后,猪表现出适度的高热。此外,接种后28天未检测到鼠伤寒沙门氏菌ΔznuABC的粪便脱落。此外,接种鼠伤寒沙门氏菌ΔznuABC引起了明显的抗沙门氏菌抗体和IFN-γ的产生。综上所述,这些结果表明鼠伤寒沙门氏菌ΔznuABC在猪体内是减毒的和免疫原性的。虽然疫苗剂量不能保证完全安全,但仍有足够的余地来建立更好的使用条件,这表明鼠伤寒沙门氏菌ΔznuABC可能是一种有前途的减毒菌株,可以用作口服粘膜活疫苗。
Meat contamination by Salmonella spp. is emerging as a major cause of human enteric infections in industrialized countries. The attempts to reduce human cases of salmonellosis encompass pre- and post-harvest interventions. In this context, vaccination of pigs may represent an effective instrument in eliminating/reducing Salmonella burden through the food chain. We have previously demonstrated that Salmonella Typhimurium lacking the ZnuABC transporter (S. Typhimurium ΔznuABC) is a promising candidate live vaccine in different mouse models of Salmonella Typhimurium infection. In this study, we confirmed in pigs the attenuation of S. Typhimurium ΔznuABC. Moreover, we evaluated the safety and immunogenicity of S. Typhimurium ΔznuABC administered to pigs by the oral route. We monitored clinical conditions of animals and we conducted a microbiological culture and a quantification of the humoral and cellular immune response, respectively, on fecal and blood samples of pigs. After vaccination with attenuated S. Typhimurium ΔznuABC, pigs showed a modest degree of hyperthermia. In addition, fecal shedding of S. Typhimurium ΔznuABC could not be detected 28 days after the inoculum. Furthermore, vaccination with S. Typhimurium ΔznuABC elicited a distinct production of anti-Salmonella antibodies and IFN-γ. Taken together, these results suggest that S. Typhimurium ΔznuABC is attenuated and immunogenic in pigs. Although the vaccine dosages do not guarantee complete safety there is ample margin to set up better conditions of use, suggesting that S. Typhimurium ΔznuABC could be a promising attenuated strain to be used as live mucosal vaccine for oral delivery.