rAd5和rAAV2／1载体疫苗诱导载体特异性和外源基因特异性免疫反应的研究

目的 在小鼠体内比较携带相同外源基因的rAd5和rAAV2/1载体疫苗诱导的载体特异性和外源基因特异性免疫应答的差异.方法 分别用携带HIV-1 gag基因的rAd5和rAAV2/1疫苗免疫BALB/c小鼠,在免疫后不同时间点用Elispot方法和ELISA方法检测小鼠体内的rAd5或rAAV2/1载体特异性及HIV-1 gag特异性细胞免疫反应和抗体反应.结果 rAd5-gag能够诱导较强的gag特异性细胞免疫反应,显著高于针对Ad5载体的细胞免疫反应;而rAAV2/1 -gag诱导的gag特异性及AAV2/1载体特异性细胞免疫反应水平都较低.rAd5-gag诱导的P24特异性和Ad5特异性IgG抗体水平都较高,并且二者相当;与rAd5-gag相比rAAV2/1 -gag可诱导更高水平的P24 IgG抗体,而且rAAV2/1 -gag诱导的P24 igG高于AAV2/1载体特异性IgG水平.结论 rAd5载体可诱导强的外源基因特异性细胞免疫和抗体反应,针对载体的细胞免疫反应较弱而抗体反应较强;rAAV2/1载体可诱导强的外源基因特异性抗体反应,明显高于针对载体的抗体反应,外源基因特异性和载体特异性细胞免疫反应水平都很低.

Study on vector-specific and foreign gene-specific immune responses induced by rAd5 and rAAV2/1 vaccines

Objective To compare the foreign gene-specific and vector-specific immune responses in BALB/c mice immunized with rAd5 or rAAV2/1 expressing the same gene.Methods BALB/c mice were immunized with rAd5-gag or rAAV2/1-gag once,HIV-1 Gag-specific and vector- specific cellular immune responses were analyzed by Elispot assay,HIV-1 P24-specifc IgG and vector-specific IgG were tested by ELISA assay.Results Mice immunized with rAd5-gag induced potent Gag-specific cellular immune responses and that were significantly higher than Ad5-specfic cellular responses,while rAAV2/1-gag elicited weak Gag-specific and AAV2/1-specific cellular responses.Both P24-specific and Ad5-specific IgG titers induced by rAd5-gag were high and in similar level.Higher level of P24-specific IgG was found in mice inoculated with rAAV2/1-gag than rAd5-gag.And the P24-specific IgG titers were higher than the vectorspecific IgG titers in mice immunized with rAAV2/1.Conclusion rAd5 could elicit strong foreign genespecific cellular and humoral immune responses,weak vector-specific cellular responses and strong vectorspecific antibodies,rAAV2/1 could induce potent foreign gene-specific antibodies that were much higher than vector-specific IgG,while both foreign gene-specific and vector-specific cellular responses were very low.