SDF-1基因对HIV-1核酸疫苗诱导的免疫应答

SDF-1 Gene Modulates Immune Responses Induced by HIV-1 Nucleic Acid Vaccine

研究SDF-1基因对HIV-1核酸疫苗诱导免疫应答的影响,以探求治疗性HIV-1核酸疫苗的新策略。将pCIneoGAG联合SDF1基因或者pCIneoGAG单独免疫Balb/c小鼠,采用ELISA检测免疫小鼠的特异性抗体和IFNγ水平,用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。研究结果提示:与pCIneoGAG免疫组比较,pCIneoGAG联合SDF-1基因免疫组小鼠血清的抗HIV-1p24抗体滴度降低,有显著性差异(p<0.01);而与pCIneoGAG免疫组比较,pCIneoGAG联合SDF-1基因免疫组小鼠血清的IFNγ升高,差异显著(p<0.01);pCIneoGAG联合SDF-1基因免疫组小鼠的脾淋巴细胞增殖实验刺激指数(SI)以及特异性CTL活性均高于pCIneoGAG免疫组,有显著性差异(p<0.01)。因此,SDF-1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,SDF-1基因对体液免疫有抑制作用。SDF-1基因对于治疗性HIV-1核酸疫苗是具有较好应用前景的免疫佐剂。

To investigate the effect of SDF-1 gene immunization on immune response induced by HIV-1(Human immunodeficiency virus) nucleic acid vaccine and to explore new strategies for therapeutic HIV DNA vaccine. Balb/c mice were immunized with pCI-neoGAG alone or co-administered with the DNA encoding for SDF-1.Their sera were 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. Our result showed that the anti-HIV antibody titers of mice co-immunized with pCI-neoGAG and the DNA encoding for SDF-1 were lower than that of mice immunized with pCI-neoGAG alone(P<0.01).The IFN-γ level of mice co-immunized with pCI-neoGAG and the DNA encoding for SDF-1was higher than that of mice immunized with pCI-neoGAG alone(P<0.01).Furthermore, compared with mice injected with pCI-neoGAG alone, the specific CTL cytotoxity activity and antigen-specific lymphoproliferative responses of mice immunized with pCI-neoGAG and the DNA encoding for SDF-1 were significantly enhanced respectively (P<0.01).Thus, the DNA encoding for SDF-1 together with HIV DNA vaccine may enhance specific Th-1 responses and cellular immune responses elicited in mice. However, the DNA encoding for SDF-1 may down-regulate the humoral responses. Hence the DNA encoding for SDF-1 are promising immune aduvants for therapeutic HIV DNA vaccine .