CpG和Al(OH)3佐剂联合使用增强丙型肝炎病毒重组蛋白疫苗的细胞免疫原性

目的 CpG和Al(OH)3佐剂联合使用增强丙型肝炎病毒(HCV)重组蛋白联合疫苗(TFE)的细胞免疫原性.方法 以CpG、Al(OH)3、Al(OH)3+CpG和弗氏佐剂(FA)为免疫佐剂,分别与TFE混合免疫BALB/c小鼠.末次免疫后10 d取静脉血,分离血清,用ELISA方法测定血清中特异性抗体,并每组处死5只小鼠,分离小鼠脾细胞,体外检测IFN-γ、IL-4和CTL杀伤试验;剩余的小鼠背部皮下注射1×106个SP2/O-NS3细胞,观察其保护作用.组间均数差异用LSD-t检验.结果 TFE+Al(OH)3+CpG组的特异性CTL杀伤能力高于TFE+FA组和TFE+CpG组(P<0.05);与TFE+Al(OH)3组和TFE+CpG组相比,TFE+Al(OH)3+CpG组小鼠脾细胞中分泌IFN-γ的淋巴细胞的数量显著增多(P<0.05).结论 Al(OH)3和CpG合用能显著增强HCV重组蛋白联合疫苗TFE的细胞免疫原性;TFE+Al(OH)3+CpG能有效预防表达HCV非结构蛋白NS3的细胞SP2/0-NS3对免疫小鼠的攻击.

Combining CpG and Al(OH)3 enhances the immunogenicity of hepatitis C virus recombinant ptotein combined vaccine

Objective To research CpG and Al(OH)3 adjuvants enhancing immunogenicity of hepatitis C virus(HCV) recombinant ptotein combined vaccine(TIE).Methods BALB/c mice were immunized with candidate vaccine TFE using CpG,Al(OH)3,Al(OH) 3 + CpG,or freund's adjuvant(FA) as the adjuvant.Five mice were sacrificed after 10 d of the last immunization.Specific antibodies in sera were tested by enzyme-linked immunosorbent assay(ELISA).Splenic cells were isolated and levels of IFN-γ,IL-4 and cytotoxic T lymphocyte(CTL) cytotoxicity assay were messuredin vitro.The remaining mice were subcutaneouly injected with 1 × 106 SP2/0-NS3 cells on the back to investigate the protective effects.The differences of means between groups were compared by LSD-t test.Results The specific CTL activity of TFE + A1(OH) 3 + CpG group was higher than TFE + FA group and TFE + CpG group(P ＜ 0.05).The level of IFN-γsecreting cells in TFE + Al(OH)3 + CpG group was higher than that in TFE + M(OH)3 group or TFE + CpG group(P ＜ 0.05).Conclusion Combining Al(OH) 3 and CpG could enhance specific cellular immunogenicity of candidate HCV vaccine TFE.TFE + M(OH) 3 + CpG could effetively prevent the attack of tumor cell SP2/0-NS3 expressing nonstructural protein NS3 of HCV.