IL-23、IL-27对RSV重组蛋白疫苗免疫原性的影响

摘要

目的:以编码IL-23和IL-27的真核表达质粒pcDNA3.1-IL-23(以下简称IL-23)和pcDNA3.1-IL-27(以下简称IL-27)为佐剂,与呼吸道合胞病毒(RSV)重组蛋白疫苗G1F/M2共免疫小鼠,观察IL-23和IL-27对疫苗的免疫原性的影响.方法:以IL-23、IL-27质粒和Al(OH)3为免疫佐剂,与G1F/M2共免疫BALB/c小鼠,末次免疫后10天杀死小鼠,用ELISA检测特异性IgG、IgG1和IgG2a水平;流式细胞术检测小鼠脾细胞CD4+、CD8+细胞的变化;用乳酸脱氢酶(LDH)释放法检测特异性小鼠脾细胞杀伤活性.结果:G1F/M2+Al(OH)3+IL-23和G1F/M2+Al(OH)3+IL-27可诱导高效价的IgG、IgG1、IgG2a抗体,且显著高于这三种佐剂单独使用诱导的抗体效价;流式细胞检测结果显示G1F/M2+IL-23和G1F/M2+Al(OH)3+IL-23刺激的CD4+T细胞和CD8+T细胞水平显著高于其他组;单独的IL-23或IL-27对G1F/M2诱导的脾细胞杀伤活性没有增强作用,而Al(OH)3+IL-23和Al(OH)3+IL-27佐剂组的杀伤率显著高于单独的IL-23、IL-27或Al(OH)3组.结论:这些结果表明:IL-23或IL-27质粒与传统铝盐佐剂Al(OH)3联合使用能显著增强RSV重组疫苗G1F/M2的免疫原性.%Objective :Mice were co-immunized with the recombinant vaccines G1F/M2 of respiratory syncytial virus (RSV ) and the adjuvant plasmids either pcDNA3.1-IL-23 or pcDNA3 .1-IL-27 to observe the effect of IL-23 or IL-27 on the immunogenity of the candidate vaccine .Methods :BALB/c mice were immunized with the recombinant vaccine encoding G1F/M2 combined with the plasmids either pcDNA3 .1-IL-23 or pcDNA3 .1-IL-27 and/or AI(OH )3 as adjuvant .Mice were killed at 10 days after the last immunization .Anti-G1F/M2 IgG , IgC1 ,IgG2a in the sera were detected by ELISA .The lymphocyte phenotype of CD4+ or CD8+ was analyzed by FCM ,and their splenocytes were tested for CTL activity by LDH-release assay .Results :GIF/M2+Al(OH )3+IL-23 and G1F/M2+Al(OH )3+ IL-27 both induced high titers of IgG ,IgG1 and IgG2a antihodies .The antibody levels of the immunized mice with G 1F/M2+Al(OH )3+IL-23 or GIF/M2+Al (OH )3+ IL-27 groups were significantly higher than those of G1F/M2+Al(OH )3 ,G1F/M2+ IL-23 , or G1F/M2+ IL-27 alone .The levels of CD4+ and CD8+T cells in the groups of G1F/M2+IL-23 and G1F/M2+Al(OH )3+ IL-23 were significantly higher than in other groups .IL-23 or IL-27 alone did not enhanced the CTL activity induced by G1F/M2 ,but immunization with G1F/M2+Al (OH )3 + IL-23 or G1F/M2+ Al(OH )3+ IL-27 induced significantly higher level of CTL than G1F/M2+Al (OH )3 ,G1F/M2+ IL-23 , or G1F/M2+ IL-27 .Conclusion : These results indicates that combining IL-23 and Al(OH )3 ,or IL-27 and AI(OH )3 could enhance the immunogenicity of candidate RSV vaccine G1F/M2 significantly .