不同佐剂对 preS2／S 乙型肝炎疫苗免疫原性的影响

摘要

目的：探讨不同佐剂对preS2/S乙型肝炎疫苗免疫原性的影响。方法将BALB/C小鼠随机分为6组：铝佐剂组（S＋Al和S2/S＋Al）、细胞因子佐剂组（S2/S＋CK1、S2/S＋CK2和S2/S＋CK3）及阴性对照组（NG），用相应抗原腹腔免疫各组小鼠，1 mL/只，分别于免疫后2、4和6周采血，分离血清，ELISA法检测血清中抗-HBs抗体和preS2抗体水平；WST-1法检测淋巴细胞增殖情况。结果免疫后2周，铝佐剂组（ S＋Al和S2/S＋Al）抗体水平较高，阳转率达100％，而细胞因子佐剂组抗-HBs抗体水平均较低，S2/S＋CK2及S2/S＋CK3组抗体阳转率为0，与NG组比较差异无统计学意义（ P＞0．05）；免疫后4周，细胞因子佐剂组抗-HBs抗体水平升高明显，铝佐剂组S2/S＋Al抗体水平显著高于S＋Al（P＜0．05）；免疫后6周，细胞因子佐剂组抗体水平高于铝佐剂组，其中S2/S＋CK1组抗体水平较高。免疫后2周，各组小鼠血清中抗-preS2抗体均达到较高水平，各组间差异均无统计学意义（P＞0．05）；免疫后4周和6周，抗体水平均有所下降，但下降不明显；铝佐剂组S＋Al和S2/S＋Al抗-preS2抗体水平差异无统计学意义（ P＞0．05）。免疫后4周，各组小鼠淋巴细胞刺激指数铝佐剂组（S＋Al和S2/S＋Al）低于细胞因子佐剂组，且差异有统计学意义（P＜0．05），其中S2/S＋CK1组淋巴细胞增殖水平较高。结论不同佐剂的preS2/S乙型肝炎疫苗均能诱导较高水平的抗-HBs和抗-preS2抗体，细胞因子佐剂组淋巴细胞增殖水平显著高于铝佐剂组，为新型乙型肝炎疫苗和治疗性乙型肝炎疫苗的研究提供了实验依据。%Objective To explore the effect of different adjuvants on Immunogenicity of preS 2/S hepatitis B vaccine . Methods BALB/C mice were randomly divided into aluminium hydroxides adjuvant (S+Al and S2/S+Al),cytokine adju-vant(S2/S+CK1,S2/S+CK2 and S2/S+CK3)and negative control(NG)groups,and immunized i.p.with the corresponding antigens for once , 1 mL/only,of which the sera were collected and determined for anti-HBs and anti-preS2 antibody level by ELISA assays on 2, 4 and 6 weeks after injection.The splenocytes of mice were collected and determined for the prolif-eration of lymphocytes by WST-1 assay at 4 weeks after injection .Results 2 weeks after injection , high anti-HBs antibody levels were induced in aluminium hydroxides adjuvant groups (S+Al and S2/S+Al), the positive rates were 100%.The anti-HBs antibody levels were lower in cytokine adjuvant groups , positive rates of anti-HBs antibody were 0 in S2/S+CK2 and S2/S+CK3 groups, which showed no difference compared with NG groups (P>0.05);4 weeks after injection, the anti-HBs antibody levels were significantly increased in cytokine adjuvant groups , the level was significantly higher in S 2/S+Al group than that of S+Al group(P<0.05);6 weeks after injection, the anti-HBs antibody levels were higher in cytokine ad-juvant groups than those of aluminium hydroxides adjuvant groups , and the higher in S2/S+CK1 group.2 weeks after injec-tion, the anti-preS2 antibody were high level in all groups , which showed no difference (P>0.05);4 and 6 weeks after in-jection, the anti-preS2 antibody levels had a small decline , which showed no significant difference between S+Al and S2/S+Al groups ( P>0 .05 ) .Lymphocytes stimulation indexes were significantly lower in aluminium hydroxides adjuvant groups than that of cytokine adjuvant groups (P<0.05), the S2/S+CK1 group was the higher .Conclusion preS2/S hepatitis B vaccine with different adjuvants could induce high level of anti-HBs and anti-preS2 antibody , the proliferation levels of lymphocytes were higher in cytokine groups than that of alu -minium hydroxides groups , It provided the experimental basis for development of new hepatitis B vaccine and therapeutic hepatitis B vaccine .