Immunogenicity and protective efficacy of a Salmonella Enteritidis sptP mutant as a live attenuated vaccine candidate.
Immunogenicity and protective efficacy of a Salmonella Enteritidis sptP mutant as a live attenuated vaccine candidate.
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DOI：
10.1186/s12917-017-1115-3
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发表时间：
2017-06-24
影响因子：
2.6
通讯作者：
Jiao X
中科院分区：
文献类型：
--
作者：
Lin Z;Tang P;Jiao Y;Kang X;Li Q;Xu X;Sun J;Pan Z;Jiao X
肠炎沙门氏菌（S. Enteritidis）是人类和动物中高度适应性的病原体。作为沙门氏菌 III 型分泌系统 (T3SS) 效应子，沙门氏菌蛋白酪氨酸磷酸酶 (SptP) 对于该属的毒力至关重要。为了研究C50336ΔsptP作为小鼠口服减毒活疫苗的可行性，我们通过λ-Red介导的重组在肠炎沙门氏菌菌株C50336中产生了sptP基因缺失突变株C50336ΔsptP，并评估了肠炎沙门氏菌sptP突变株C50336ΔsptP对小鼠沙门氏菌病的保护能力。我们发现 C50336ΔsptP 在小鼠中是一种高免疫原性、有效且安全的疫苗。与野生型 C50336 相比，C50336ΔsptP 显示出毒力降低，经口服感染小鼠的 50% 致死剂量 (LD50) 证实。 C50336ΔsptP 还显示体内和体外细菌定植减少。与用磷酸盐缓冲盐水 (PBS) 处理的对照动物相比，用 C50336ΔsptP 进行免疫对体重没有显着影响，也没有导致明显的临床症状，但在接种后 12 天和 26 天诱导了体液和细胞免疫反应。每只小鼠使用 1 × 108 菌落形成单位 (CFU) C50336ΔsptP 进行免疫，可对随后野生型 C50336 菌株的攻击提供 100% 的保护，并且与对照组相比，免疫小鼠表现出轻微和暂时的临床症状。这些结果表明 C50336ΔsptP 可以作为沙门氏菌病口服减毒活疫苗。
Salmonella enterica serovar Enteritidis (S. Enteritidis) is a highly adaptive pathogen in both humans and animals. As a Salmonella Type III secretion system (T3SS) effector, Salmonella protein tyrosine phosphatase (SptP) is critical for virulence in this genus. To investigate the feasibility of using C50336ΔsptP as a live attenuated oral vaccine in mice, we generated the sptP gene deletion mutant C50336ΔsptP in S. Enteritidis strain C50336 by λ-Red mediated recombination and evaluated the protective ability of the S. Enteritidis sptP mutant strain C50336ΔsptP against mice salmonellosis. We found that C50336ΔsptP was a highly immunogenic, effective, and safe vaccine in mice. Compared to wild-type C50336, C50336ΔsptP showed reduced virulence as confirmed by the 50% lethal dose (LD50) in orally infected mice. C50336ΔsptP also showed decreased bacterial colonization both in vivo and in vitro. Immunization with C50336ΔsptP had no significant effect on body weight and did not result in obvious clinical symptoms relative to control animals treated with phosphate-buffered saline (PBS), but induced humoral and cellular immune responses at 12 and 26 days post inoculation. Immunization with 1 × 108 colony-forming units (CFU) C50336ΔsptP per mouse provided 100% protection against subsequent challenge with the wild-type C50336 strain, and immunized mice showed mild and temporary clinical symptoms as compared to those of control group. These results demonstrate that C50336ΔsptP can be a live attenuated oral vaccine for salmonellosis.