趋化因子基因对HIV-1外膜蛋白基因疫苗诱导的免疫应答的影响

Chemokine Genes Modulate Immune Responses Induced by HIV-1 Envelope Protein Gene Vaccine

研究趋化因子基因对HIV-1外膜蛋白基因疫苗诱导免疫应答的影响,以探求防治HIV的新策略。将 pVAX1GP120联合RANTES、MIP-1α基因或者pVAX1GP120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,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。与pVAX1GP120免疫组比较,pVAX1GP120联合RANTES、MIP- 1α基因免疫组小鼠血清的抗HIV-1gp120抗体滴度升高,有显著性差异(p<0．01);与pVAX1GP120免疫组比较, pVAX1GP120联合RANTES、MIP-1α基因免疫组小鼠血清的IFN-γ升高,有显著性差异(p<0．01); pVAX1GP120联合RANTES、MIP-1α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pVAX1GP120免疫组,有显著性差异(p<0．01)。RANTES、MIP-1α基因联合HIV-1外膜蛋白基因疫苗免 疫小鼠,可能增强HIV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外膜蛋白基因疫苗具有较好应用前景的免疫佐剂。

To investigate the effect of chemokine gene immunization on immune responses induced by HIV-1 envelope protein gene vaccine and to explore new strategies against HIV, Balb/c mice were immunized with pVAX1GP120 alone or co-administered with the DNA encoding for RAN- TES、and MIP-1α. Their sera were collected for analyzing anti-HIV antibody and IFN-γ by ELISA, and splenocytes of Balb/c mice were isolated for detecting antigen-specific lymphoprolif- erative responses and specific CTL response by MTT and LDH assays, respectively. Our results showed that the anti-HIV antibody thers of mice co-immunized with pVAX1GP120 and the DNA encoding for RANTES and MIP-1α were higher than that of mice immunized with pVAX1GP120 alone （P（0.01）. The IFN-γ level of mice co-immunized with pVAX1GP120 and the DNA encoding for RANTES and MIP-1α was higher than that of mice immunized with pVAX1GP120 alone （P（0.01）. In comparison with mice injected with pVAX1GP120 alone, the specific CTL cytotoxity activity and antigen-specific lymphoproliferative responses of mice immunized with pVAX1GP120 and the DNA encoding for RANTES and MIP-1α were significantly enhanced （P〈0.01）. The DNA encoding for RANTES and MIP-1α together with HIV-1 envelope nucleic acid vaccine may enhance HIV-1 specific Th-1 responses and cellular immune responses elicited in mice and may up-regulate the humoral responses. The DNA encoding for RANTES and MIP-1α are promising immune adjuvant for HIV-1 envelope nucleic acid vaccine.