质粒稳定性对鼠伤寒沙门氏菌口服DNA递送的影响。
Impact of plasmid stability on oral DNA delivery by Salmonella enterica serovar Typhimurium.
作者信息
Gahan Michelle E, Webster Diane E, Wesselingh Steven L, Strugnell Richard A
机构信息
Children's Vaccines Unit, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3001, Australia.
出版信息
Vaccine. 2007 Feb 9;25(8):1476-83. doi: 10.1016/j.vaccine.2006.10.042. Epub 2006 Nov 7.
Live attenuated Salmonellae may overcome limitations with conventional methods of DNA immunisation. This study examined the impact of plasmid stability on oral DNA delivery by the attenuated Salmonella enterica serovar Typhimurium vaccine strain BRD509. A DNA vaccine cassette comprising the C fragment of tetanus toxin under control of the cytomegalovirus (CMV) promoter was ligated into plasmid pcDNA3, pUC18, pBBR122, pACYC184, pRSF1010/CAT, pBR322 and pAT153. In vitro and in vivo stability studies revealed that, with the exception of pcDNA3 and pUC18, the plasmids were retained by BRD509. However, pAT153 was the only plasmid to induce a tetanus toxoid-specific antibody response following oral delivery. Plasmid copy number was found to impact on plasmid stability and the induction of antigen-specific humoral responses.
减毒活沙门氏菌可能克服传统DNA免疫方法的局限性。本研究检测了质粒稳定性对减毒肠炎沙门氏菌血清型鼠伤寒疫苗株BRD509口服DNA递送的影响。将包含在巨细胞病毒（CMV）启动子控制下的破伤风毒素C片段的DNA疫苗盒连接到质粒pcDNA3、pUC18、pBBR122、pACYC184、pRSF1010/CAT、pBR322和pAT153中。体外和体内稳定性研究表明，除了pcDNA3和pUC18外，BRD509能保留这些质粒。然而，pAT153是口服递送后唯一能诱导破伤风类毒素特异性抗体反应的质粒。发现质粒拷贝数会影响质粒稳定性和抗原特异性体液反应的诱导。
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