...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >Construction and Characterization of a Live, Attenuated aroA Deletion Mutant of Pseudomonas aeruginosa as a Candidate Intranasal Vaccine
【24h】

Construction and Characterization of a Live, Attenuated aroA Deletion Mutant of Pseudomonas aeruginosa as a Candidate Intranasal Vaccine

机译：铜绿假单胞菌作为候选鼻内疫苗的减毒aroA缺失突变体的构建和表征

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Antibodies to the lipopolysaccharide O antigen of Pseudomonas aeruginosa mediate high-level immunity, but protective epitopes have proven to be poorly immunogenic, while nonprotective or minimally protective O-antigen epitopes often elicit the best immune responses. With the goal of developing a broadly protective P. aeruginosa vaccine, we used a gene replacement system based on the Flp recombinase to construct an unmarked aroA deletion mutant of the P. aeruginosa serogroup O2/O5 strain PAO1. The resultant aroA deletion mutant of PAO1 is designated PAO1ΔaroA. The aroA deletion was confirmed by both PCR and failure of the mutant to grow on minimal media lacking aromatic amino acids. When evaluated for safety and immunogenicity in mice, PAO1ΔaroA could be applied either intranasally or intraperitoneally at doses up to 5 × 109 CFU per mouse without adverse effects. No dissemination of PAO1ΔaroA to blood, liver, or spleen was detected after intranasal application, and histological evidence of pneumonia was minimal. Intranasal immunization of mice and rabbits elicited high titers of immunoglobulin G to whole bacterial cells and to heat-stable bacterial antigens of all seven prototypic P. aeruginosa serogroup O2/O5 strains. The mouse antisera mediated potent phagocytic killing of most of the prototypic serogroup O2/O5 strains, while the rabbit antisera mediated phagocytic killing of several serogroup-heterologous strains in addition to killing all O2/O5 strains. This live, attenuated P. aeruginosa strain PAO1ΔaroA appears to be safe for potential use as an intranasal vaccine and elicits high titers of opsonic antibodies against multiple strains of the P. aeruginosa O2/O5 serogroup.
机译：铜绿假单胞菌脂多糖O抗原的抗体可介导高水平的免疫力，但保护性抗原决定簇的免疫原性较弱，而非保护性或保护性最低的O抗原抗原决定簇通常可引起最佳的免疫反应。以开发具有广泛保护性的 P为目标。在铜绿假单胞菌疫苗中，我们使用了基于Flp重组酶的基因替换系统，构建了一个未标记的 P的 aroA 缺失突变体。铜绿菌O2 / O5血清型PAO1。所得的PAO1的 aroA 缺失突变体称为PAO1Δ aroA 。通过PCR和突变体不能在缺乏芳香族氨基酸的基本培养基上生长来确认 aroA 缺失。当评估小鼠的安全性和免疫原性时，PAO1Δ aroA 可以鼻内或腹膜内施用，每只小鼠的最高剂量为5×10 9 CFU，而无不良反应。经鼻内应用后，未发现PAO1Δ aroA 散布到血液，肝脏或脾脏，并且肺炎的组织学证据极少。小鼠和兔子的鼻内免疫引发了针对整个细菌细胞和所有七个原型 P的热稳定细菌抗原的高滴度免疫球蛋白G。铜绿菌O2 / O5血清群。小鼠抗血清介导了大多数原型O2 / O5血清型菌株的吞噬杀死，而兔抗血清介导了除杀死所有O2 / O5菌株以外的几种血清组-异源菌株的吞噬杀死。此实时衰减的 P。铜绿假单胞菌PAO1Δ aroA 似乎可以安全地用作鼻内疫苗，并引起高滴度针对多种 P菌株的调理抗体。铜绿O2 / O5血清群。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号