Salmonella synthesizing 1-dephosphorylated [corrected] lipopolysaccharide exhibits low endotoxic activity while retaining its immunogenicity.
Salmonella synthesizing 1-dephosphorylated [corrected] lipopolysaccharide exhibits low endotoxic activity while retaining its immunogenicity.
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DOI：
10.4049/jimmunol.1100339
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发表时间：
2011-07-01
期刊：
影响因子：
--
通讯作者：
Curtiss R 3rd
中科院分区：
文献类型：
--
作者：
Kong Q;Six DA;Roland KL;Liu Q;Gu L;Reynolds CM;Wang X;Raetz CR;Curtiss R 3rd
安全的减毒沙门氏菌活疫苗的开发可通过其脂多糖的解毒来促进。最近对来自土拉弗朗西斯菌的脂质A 1-磷酸酶（LpxE）的表征使我们能够构建重组、无质粒的沙门氏菌菌株，该菌株主要产生1-脱磷酸化脂质A，类似于批准用于人类的佐剂。在低pH、低Mg 2+培养条件下也证实了完全的脂质A1-去磷酸化，这诱导脂质A修饰。沙门氏菌中的lpxE表达将其在小鼠中的毒力降低了五个数量级。此外，接种这些脱毒菌株的小鼠可免受野生型攻击。合成肺炎球菌表面蛋白A（PspA）的候选沙门氏菌疫苗菌株也被证实具有几乎完全的脂质A1-去磷酸化。在接种LpxE/PspA菌株后，小鼠产生了稳健水平的抗PspA抗体，并且与仅用载体免疫的小鼠相比，针对野生型肺炎链球菌WU 2的攻击显示出显著改善的存活率，验证了沙门氏菌合成1-脱磷酸化脂质A作为抗原递送系统。
The development of safe live, attenuated Salmonella vaccines may be facilitated by detoxification of its lipopolysaccharide. Recent characterization of the lipid A 1-phosphatase, LpxE, from Francisella tularensis allowed us to construct recombinant, plasmid-free strains of Salmonella that produce predominantly 1-dephosphorylated lipid A, similar to the adjuvant approved for human use. Complete lipid A 1-dephosphorylation was also confirmed under low pH, low Mg2+ culture conditions, which induce lipid A modifications. lpxE expression in Salmonella reduced its virulence in mice by five orders of magnitude. Moreover, mice inoculated with these detoxified strains were protected against wild-type challenge. Candidate Salmonella vaccine strains synthesizing pneumococcal surface protein A (PspA) were also confirmed to possess nearly complete lipid A 1-dephosphorylation. After inoculation by the LpxE/PspA strains, mice produced robust levels of anti-PspA antibodies and showed significantly improved survival against challenge with wild-type Streptococcus pneumoniae WU2 as compared to vector-only immunized mice, validating Salmonella synthesizing 1-dephosphorylated lipid A as an antigen delivery system.
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影响因子：
6.4
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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