Levels of expression and immunogenicity of attenuated Salmonella enterica serovar typhimurium strains expressing Escherichia coli mutant heat-labile enterotoxin
Levels of expression and immunogenicity of attenuated Salmonella enterica serovar typhimurium strains expressing Escherichia coli mutant heat-labile enterotoxin
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DOI：
10.1128/iai.66.1.224-231.1998
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发表时间：
1998-01-01
影响因子：
3.1
通讯作者：
Galeotti, CL
中科院分区：
文献类型：
--
作者：
Covone, MG;Brocchi, M;Galeotti, CL
分析了外源基因剂量以及鼠伤寒沙门氏菌菌株变异性对针对异源抗原、大肠杆菌不耐热肠毒素LTK 63的无毒突变体和载体沙门氏菌菌株的免疫应答的影响。两种不同血清型UK-1和SR-11的鼠伤寒沙门氏菌Δ cya Δ crp Δ asd菌株。发现在体外不同沙门氏菌分离株中肠毒素的表达变化很大，并且对于附加型载体，与质粒拷贝数相关，LTK 63特异性血清免疫球蛋白G（IgG）和粘膜免疫球蛋白A（伊加）抗体在用高水平-表达菌株。发现高抗LTK 63 IgG和伊加滴度对应于较高的抗沙门氏菌免疫，表明LTK 63对对载体的应答发挥佐剂作用。在以相同速率产生抗原的减毒Delta cya Delta crp UK-I和SR-II衍生物免疫的小鼠组之间，观察到抗LTK 63免疫反应存在统计学显着差异。这些数据表明，不同遗传背景的鼠伤寒沙门氏菌菌株中的相同减毒可以显着影响对异源抗原的免疫反应。此外，通过减毒S.鼠伤寒沙门氏菌株只有在入侵的初始阶段抗原合成非常高时才有效，而S.深层组织中的鼠伤寒沙门氏菌菌株仅具有边缘影响。
The effects of heterologous gene dosage as well as Salmonella typhimurium strain variability on immune response toward both the heterologous antigen, the nontoxic mutant of the Escherichia coli heat-labile enterotoxin LTK63, and the carrier Salmonella strain have been analyzed, Effects of a single integration into the host DNA and different-copy-number episomal vectors were compared in S. typhimurium Delta cya Delta crp Delta asd strains of two different serotypes, UK-1 and SR-11, Expression of the enterotoxin in the different Salmonella isolates in vitro was found to vary considerably and, for the episomal vectors, to correlate with the plasmid copy number, LTK63-specific serum immunoglobulin G (IgG) and mucosal immunoglobulin A (IgA) antibodies were highest in mice immunized with the high-level-expression strain. High anti-LTK63 IgG and IgA titers were found to correspond to higher anti-Salmonella immunity, suggesting that LTK63 exerts an adjuvant effect on response to the carrier. Statistically significant differences in anti-LTK63 immune response were observed between groups of mice immunized with the attenuated Delta cya Delta crp UK-I and SR-II derivatives producing the antigen at the same rate, These data indicate that the same attenuation in S, typhimurium strains of different genetic backgrounds can influence significantly the immune response toward the heterologous antigen. Moreover, delivery of the LTK63 enterotoxin to the immune system by attenuated S. typhimurium strains is effective only when synthesis of the antigen is very high during the initial phase of invasion, while persistence of the S. typhimurium strain in deep tissues has only marginal influence.