HIV-1疫苗prime-boost策略免疫间隔研究

目的探索不同的DNA、重组痘苗病毒、蛋白疫苗免疫间隔在HIV-1疫苗prime-boost策略中对免疫效果的影响,为建立最佳免疫方案提供理论支持。方法对小鼠进行3针DNA初免,之后分别间隔3周、6周、12周、16周免疫重组痘苗病毒VTKgpe;对小鼠或兔子进行3针DNA初免,间隔16周免疫VTKgpe,之后分别间隔4周或8周免疫gp140蛋白。末次免疫后2周检测HIV-1特异性体液或细胞免疫应答。结果 DNA初免-VTKgpe加强间隔16周效果最佳,诱导的HIV-1 Env特异性抗体滴度达到105,分泌IFN-γ的T细胞数为5 966.4/106细胞。DNA初免,间隔16周VTKgpe加强,之后间隔4周或8周gp140蛋白加强效果差异无统计学意义。结论 DNA疫苗初免,16周后VTKgpe加强,4周后gp140蛋白加强可诱导较高的免疫应答,同时更为适宜临床试验及商业化应用的需要。

Effect of prime-boost strategy of interval immunization with HIV-1 vaccine on the immune reponse

Objective To investigate the effect of various immunization interval of DNA,recombinant VTT and protein in HIV-1 vaccine prime-boost strategy on immune reponse.Methods DNA vaccine priming thrice,then VTKgpe boost once 3,6,12 or 16 weeks later in mice;DNA vaccine priming thrice,VTKgpe boost once 16 weeks later,then gp140 boost once 4 or 8 weeks later.HIV-1 specific humoral and cellular immune responses were detected two weeks after the last administration.Results DNA vaccine priming thrice followed by VTKgpe 16 weeks later elicited strongest humoral and cellular responses.The gp120 specific binding antibody titer reached 105,and IFN-γ＋ T cells was 5966.4/million cells.Meanwhile,DNA vaccine priming thrice followed by VTKgpe 16 weeks later,then gp140 protein boost 4 or 8 weeks later induced almost the same immune responses.Conclusions DNA vaccine priming thrice followed by VTKgpe 16 weeks later,then gp140 protein boost after 4 weeks could induce better immune responses,suitable for clinical trial and commercialization.