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目的:用HIV-1复制型DNA疫苗和非复制型重组痘苗病毒疫苗(rNTV-C)进行单独免疫和联合免疫的研究(2种疫苗分别包含HIV-1 B’/C亚型的gp160、gag-pol、rev-tat-nef等6种基因),以了解这2种新型HIV疫苗单独免疫及联合免疫的效果,并为临床免疫方案的制定提供实验依据。方法:将HIV-1 DNA疫苗和rNTV-C疫苗免疫BALB/c小鼠,设计rNTV-C单独免疫组、DNA单独免疫组,以及DNA初免、rNTV-C加强的联合免疫组,并设计不同免疫途径和不同剂量的各种组合。用IFN-γELISPOT检测各组的细胞免疫效果,用统计学方法分析比较各组细胞免疫效果的差异。结果:DNA疫苗和rNTV-C疫苗单独免疫时,二者都能诱发针对各抗原的特异性免疫反应;联合免疫能够诱发比DNA或rNTV-C单独免疫都强的特异性细胞免疫反应。统计分析显示,2种疫苗采用肌肉注射途径的免疫效果显著高于皮内注射,1μg和5μg DNA疫苗的免疫效果差异不显著,而1×108 PFU的rNTV-C比2×107PFU的免疫效果要强。结论:联合免疫策略能够显著增强HIV-1疫苗各抗原的免疫原性,通过对2种HIV-1疫苗单独免疫及二者联合免疫的细胞免疫反应的分析比较,确定了较好的免疫方案,为疫苗临床前免疫效果评价和临床方案的制定提供了实验依据。
PURPOSE: To study the immunization and co-immunization of HIV-1 replicative DNA vaccines and non-replicating recombinant vaccinia virus (rNTV-C) (two vaccines, each containing gp160, gag -pol, rev-tat-nef, etc.) to understand the effect of immunization and combined immunization of these two new HIV vaccines, and to provide experimental evidence for the development of clinical immunization programs. Methods: BALB / c mice immunized with HIV-1 DNA vaccine and rNTV-C vaccine were designed and immunized with rNTV-C alone, DNA alone and combined with DNA prime and rNTV-C respectively Immunizations and various combinations of different doses. IFN-γELISPOT cells were used to detect the effect of cellular immunity, and statistical methods were used to analyze the difference of cell immune effects in each group. RESULTS: Both DNA vaccines and rNTV-C vaccines elicited specific immune responses against each antigen when immunized alone; combination immunization induced specific cellular immune responses that were stronger than either DNA or rNTV-C alone. The statistical analysis showed that the immunization effect of the two vaccines by intramuscular injection was significantly higher than that of intradermal injection, and the immunological effects of 1μg and 5μg DNA vaccines were not significantly different, while the immune effect of rNTV-C at 1 × 108 PFU was stronger than that of 2 × 107PFU . Conclusion: The combined immunization strategy can significantly enhance the immunogenicity of each antigen of HIV-1 vaccine. Through the comparison and analysis of the cellular immune responses between the two immunized HIV-1 vaccines and their combined immunization, the better immunization program was determined, It provides the experimental evidence for the evaluation of preclinical immune effect and the formulation of clinical protocols.