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针对HBV感染的治疗性DNA疫苗虽然具有很好的应用前景,但目前抗病毒效果并不高,表明在病毒长期感染过程中存在免疫抑制机制。以HBV的表面蛋白(HBsAg)和核心蛋白(HBcAg)为DNA疫苗抗原,采用gp96和HSP70作为佐剂联合电转以提高疫苗的活性。将gp96为佐剂的HBsAg/HBcAg DNA疫苗免疫HBV转基因鼠后引发抗原特异性的细胞免疫和体液免疫应答。使用gp96和HSP70佐剂引起Treg下调20%。与没有免疫的小鼠相比,以gp96和HSP70为佐剂的DNA疫苗显著降低血清中病毒S抗原水平和DNA拷贝数,大幅降低小鼠肝脏中HBc的表达。该研究为设计以gp96为佐剂的乙肝治疗性DNA疫苗提供了依据。
Although the therapeutic DNA vaccine against HBV infection has good application prospects, the current anti-virus effect is not high, indicating that there is an immunosuppressive mechanism during long-term virus infection. The HBsAg and HBcAg DNA vaccine antigens were used to improve the vaccine activity by using gp96 and HSP70 as adjuvants. Immunization of HBV transgenic mice with gp96-adjuvanted HBsAg / HBcAg DNA vaccine elicits antigen-specific cellular and humoral immune responses. Tregs were down-regulated by 20% using gp96 and HSP70 adjuvants. DNA vaccines adjuvanted with gp96 and HSP70 significantly reduced viral S antigen levels and DNA copy number in serum compared to non-immunized mice, dramatically reducing HBc expression in mouse livers. This study provided the basis for the design of hepatitis B therapeutic DNA vaccine adjuvanted with gp96.