HIV-1结构蛋白gag-gp120与白细胞介素2联合基因免疫

在真核表达载体pVAX1中的CMV启动子下游插入IL-2基因,构建真核表达质粒pVAXIL2。将它与表达I型人免疫缺陷病毒(Humanimmunodeficiencyvirus1,HIV-1)gag-gp120的核酸疫苗质粒pVAXGE共同肌肉注射BALB/c小鼠,免疫3次后,以ELISA法检测免疫小鼠血清中抗HIV-1抗体水平,结果显示联合免疫组小鼠在免疫2周后已有抗体产生,6周后进入高峰。乳酸脱氢酶释放法检测免疫小鼠脾特异性CTL杀伤活性,结果显示联合免疫组小鼠脾特异性CTL杀伤活性显著高于pVAXGE单独免疫组(P<0.05)和载体质粒pVAX1对照组(P<0.01)。以上结果表明:HIV-1核酸疫苗质粒pVAXGE与真核表达质粒pVAXIL2联合免疫可诱导特异性体液免疫和细胞免疫应答,且免疫应答水平高于pVAXGE单独免疫组,IL-2发挥了免疫佐剂的作用,增强了核酸疫苗的免疫原性。

Co-inoculating DNA Vaccine of HIV-1 gag-gp120 and IL-2

Eukaryotic expression plasmid pVAXIL2 was constructed by inserting IL-2 gene into the downstream of CMV (cytomegalovirus) promotor in the vector pVAX1. BALB/c mice were co-inoculated muscularly by this plasmid and the nucleic acid vaccine plasmid pVAXGE expressing the HIV-1 (Human immunodeficiency virus type I) gag-gp120 protein. The level of serum antibodies after immunization showed that the specific antibodies against HIV-1 appeared at the second week and raised to the peak level at the sixth week for the co-immunization group. The specific CTL cytotoxicity activities examined by non-radioactive lactate dehydrogenase release cytotoxity assays demonstrated that the specific CTL cytotoxicity activities in co-immunization group were significantly higher than those in pVAXGE immunization group(P<0.05) and pVAX1 control group(P<0.01). These results manifested that specific humoral and cellular immune response can be induced by co-inoculating DNA vaccine of HIV-1 gag-gp120 and IL-2, and the level of immune response in co-immunization group was higher than pVAXGE immunization group, which shows that IL-2 augments the immunogenicity of the nucleic acid vaccine as the immunoadjuvant.