基因枪接种乙型肝炎表面抗原促进DNA疫苗诱生的免疫应答转换

Th2 immunity to HBsAg primed by gene gun DNA vaccination can be shifted towards Th1 immunity by co-delivery or co-expression of HBV core gene

目的为了克服基因枪接种乙型肝炎表面抗原(HBsAg)DNA疫苗诱生的免疫应答以Th2为主的缺点,在基因枪接种质粒HBsAg DNA疫苗的同时共导入或共表达乙型肝炎病毒壳(HBV core)基因作为佐剂,以促进其所诱生的HBsAg特异性的Th2型免疫应答向Tn1型转换。方法构建可单独或共同表达HBsAg或核心抗原(HBcAg)的DNA免疫用载体pIRKS／core、pIRES／C149、pIRES／S、pIRES／S／Core和pIRES／S／C149,并在真核细胞进行表达验证。对BALB／c雌鼠进行免疫并检测小鼠免疫后的特异性体液免疫和细胞免疫指标。结果共导入或共表达HBV core基因能增强基因枪接种HBsAg DNA疫苗诱生的Th1型免疫应答水平,包括HBsAg特异的IgG2a应答、CTL活性、IFN-γ产生能力等。结论以HBV core基因为佐剂能促进基因枪接种HBsAg DNA疫苗诱生的Th2型免疫应答向Th1型免疫应答转换。

Objective To investigate the potential of co-expression or co-delivery of HBV core gene with plasmid DNA to shift HBsAg-specific Th2 immune response induced by gene-gun to Thl type. Methods pIRES/Core, pIRES/C149, pIRES/S, pIRES/S/Core and pIRES/S/C149 were constructed and expression of recombinant plasmids were confirmed in eukaryotic cells. BALB/c mice were immunized by gene-gun. After being boosted twice, humoral and cellular immunities in immunized mice were monitored. Results HBV core gene enhanced the HBsAg-specific Th1 type immune responses in gene-gun-DNA-immunized BALB/c mice, including increasing the titer of IgG2a, ratio of IgG2a/IgG1, CTL activity as well as IFN-γ secretion. Conclusion Co-delivery or co-expression of HBV core gene with HBsAg DNA vaccine by gene gun can shift the HBsAg-specific Th2 immune response to Th1 type.