优化密码对牛乳头瘤病毒L1基因粘膜免疫的增强作用

为探讨优化密码对牛乳头瘤病毒 1型主要晚期基因 (BPV1L1)免疫原性的影响 ,分别将含野生型和优化密码的人源化BPV1L1基因的真核表达质粒转入减毒沙门菌S BRD5 0 9后 ,通过滴鼻、阴道免疫、静脉注射、腹腔注射等途径免疫小鼠 ,经VLPELISA方法测定抗L1构象性抗体产生 ,MTT法观察诱导的特异性细胞免疫反应。抗体检测结果显示 ,经粘膜免疫途径 ,与含有野生型L1基因的表达质粒pcDNA3WBPVL1相比 ,含优化密码L1基因的pcDNA3HBPVL1诱导产生的SIgA、IgG明显升高 ,而细胞免疫反应无明显差异。表明优化密码能促进乳头瘤病毒晚期基因L1诱导的体液免疫反应 ,减毒沙门菌是PVL1DNA疫苗粘膜免疫的有效载体。

The Enhancement Effect of Codon Usage Optimization on the Mucosal Immuniza-tion with Bovine Papillomavirus Gene L1

To investigate the influence of codon usage optimization on the mucosal immunization with bovine papillomavirus gene L1,a live attenuated AroA, AroD autotrophic mutant of Salmonella typhimurium (S.BRD509) was used as carrier of eukaryotic expression vector (pcDNA3HBPVL1,pcDNA3WBPVL1),and inoculated into BALB/c by intraperitoneal,intranasal,intravaginal and intravenous routes. VLP-ELISA was used to detect the L1-conformational antibody and MTT method was used to observe the induced specific cell-mediated immune responses. The results showed that levels of IgG and SIgA of the mice immunized with pcDNA3HBPVL1 were higher than those of mice immunized with pcDNA3WBPVL1,but there was no any effect on cell-mediated immune responses. These results suggest that the optimized codon usage contributes to the enhancement of humoral immune responses induced by immunization with bovine papillomavirus L1 gene,and the attenuated Salmonella typhimurium may be an effective carrier for the mucosal immunization with DNA vaccine.