RANTES和MIP-1α基因对HIV-1核酸疫苗诱导免疫应答的影响

Modulation of cellular and humoral immune responses to a HIV-1 nucleic acid vaccine by RANTES,MIP-1α gene immunization

目的 研究RANTES(活化T细胞调节的、正常T细胞表达和分泌的分子 )、MIP 1α(巨噬细胞炎症蛋白 1α)基因对HIV 1核酸疫苗诱导免疫应答的影响 ,以探求HIV 1核酸疫苗的新策略。方法 pCI neoGAG联合RANTES、MIP 1α基因或者pCI neoGAG单独免疫BALB c小鼠 ,采用ELISA检测免疫小鼠的特异性抗体和IFN γ水平 ,以MTT比色法检测免疫小鼠脾淋巴细胞的增殖 ,用乳酸脱氢酶 (LDH)试验检测小鼠特异性细胞毒性T淋巴细胞 (CTL)的应答。结果 与pCI neoGAG免疫组比较 ,pCI neoGAG联合RANTES、MIP基因免疫组小鼠血清的抗HIV 1p2 4抗体滴度升高 ,IFN γ升高 ,小鼠的脾淋巴细胞增殖实验刺激指数 (SI)以及特异性CTL活性均高 ,差异都有显著性 (P <0 .0 1)。结论 RANTES、MIP 1α基因联合HIV 1核酸疫苗免疫小鼠 ,可能增强特异性TH1细胞和CTL反应 ,RANTES、MIP 1α基因对体液免疫有加强作用。因此 ,RANTES、MIP 1α基因对于HIV 1核酸疫苗是具有较好应用前景的免疫佐剂。

ObjectiveTo investigate the effect of RANTES (regulated-upon-activation,normal T cells expressed and secreted),MIP-1α (macrophage inflammatory protein-1α) gene immunization on immune response induced by HIV-1 nucleic acid vaccine (DNA vaccine)and to explore new strategies for the development of HIV DNA vaccine. MethodsBALB/c mice were immunized with pCI-neoGAG alone or co-administered with the DNA encoding for RANTES,MIP-1α. Their serum was collected for analyzing anti-HIV antibody and IFN-γ by ELISA,and splenocytes were isolated for detecting antigen-specific lymphoproliferative responses and specific CTL response by MTT assay and LDH assay respectively. ResultsThe anti-HIV titers,IFN-γ level,specific CTL cytotoxicity activity and antigen-specific lymphoproliferative response of mice co-immunized with pCI-neoGAG and the DNA encoding for RANTES,MIP-1α were higher than those in mice immunized with pCI-neoGAG alone(P<0.01). ConclusionThe DNA encoding for RANTES,MIP-1α together with HIV DNA vaccine may enhance specific T_H1 responses and cellular immune responses elicited in mice. Moreover,the DNA encoding for RANTES,MIP-1α may up-regulate the humoral responses. Hence,the DNA encoding for RANTES,MIP-1α are promising immune adjuvants for HIV DNA vaccine.