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目的对共表达的含前S1(PreS1)和前S2(PreS2)表位的乙肝表面抗原(SS1S2)及分别表达的含PreS1表位乙肝表面抗原(SS1)和含PreS2表位乙肝表面抗原(SS2)混合物的免疫原性及抗原活性进行比较,为疫苗配方的选择提供依据。方法将SS1S2抗原、SS1抗原与SS2抗原的混合物(1∶1混合,以下简称SS1+SS2)分别用氢氧化铝佐剂吸附,制成SS1S2疫苗和SS1+SS2疫苗,总抗原含量均为20μg/ml,分别经BALB/c小鼠腹腔单次注射两种疫苗1.0、0.25和0.06μg,免疫后1、2、4周采血,分离血清,ELISA法检测小鼠血清中HBV S、PreS1和PreS2抗体水平。分别以纯化的SS1抗原或SS2抗原为参考品,采用ELISA法检测6批SS1S2抗原所对应的SS1或SS2抗原含量。结果免后1、2、4周,3个剂量的SS1S2疫苗S抗体阳转率均高于同剂量的SS1+SS2疫苗,0.25μg剂量的SS1S2疫苗PreS1抗体阳转率高于同剂量的SS1+SS2疫苗;免后1、2周,3个剂量的SS1S2疫苗PreS2抗体阳转率与SS1+SS2疫苗相近;免后4周,1.0和0.25μg剂量的SS1S2疫苗PreS2抗体阳转率高于SS1+SS2疫苗。免后4周,3个剂量的SS1S2疫苗的S和PreS1几何抗体平均滴度(GMT)均高于同剂量的SS1+SS2疫苗;1.0和0.25μg剂量的SS1S2疫苗的PreS2抗体GMT高于同剂量的SS1+SS2疫苗。6批SS1S2抗原中,每10μg SS1S2抗原所包含的PreS1抗原活性相当于(12.1±0.84)μg的SS1,每10μg SS1S2抗原所包含的PreS2抗原活性相当于(7.0±0.52)μg的SS2;SS1S2抗原中SS1和SS2抗原活性之和远超过100%。结论共表达的SS1S2抗原比单独表达的SS1抗原、SS2抗原具有更强的免疫原性;共表达的SS1S2抗原中PreS1和PreS2抗原活性也得到增强。
Objective To investigate the expression of hepatitis B surface antigen (SS1S2) containing PreS1 and PreS2 epitope and the expression of hepatitis B surface antigen (SS1) ) Mixture of immunogenicity and antigen activity compared to provide the basis for the choice of vaccine formulations. Methods SS1S2 antigen, SS1 antigen and SS2 antigen mixture (1: 1, hereinafter referred to as SS1 + SS2) were adsorbed with aluminum hydroxide adjuvant to make SS1S2 vaccine and SS1 + SS2 vaccine, the total antigen content of 20μg / ml respectively. The BALB / c mice were injected intraperitoneally with 1.0, 0.25 and 0.06 μg of the two vaccines respectively, and the blood was collected at 1, 2 and 4 weeks after immunization. Serum samples of serum HBV S, PreS1 and PreS2 Level. Purified SS1 antigen or SS2 antigen were used as reference materials respectively, and the contents of SS1 or SS2 antigen corresponding to the six batches of SS1S2 antigen were detected by ELISA. Results The positive rate of S antibody of SS1S2 vaccine was higher than that of SS1 + SS2 vaccine at the same dose for 1, 2, 4 weeks and 4 weeks after vaccination. The positive rate of PreS1 antibody of SS1S2 vaccine was higher than that of SS1 + SS2 vaccine at SS1S2 and SS1 + SS2 at 3 and 4 weeks after the first and second week respectively. The positive rate of PreS2 antibody of SS1S2 vaccine at 1.0 and 0.25μg was higher than SS1 + SS2 vaccine. At 4 weeks after vaccination, the mean S and PreS1 geometric mean titers (GMTs) of the three SS1S2 vaccines were higher than those of the same dose of SS1 + SS2 vaccine. The PreS2 antibody GMTs of 1.0 and 0.25 μg SS1S2 vaccines were higher than the same dose SS1 + SS2 vaccine. The PreS1 antigen activity contained in each of the six batches of SS1S2 antigens corresponded to (12.1 ± 0.84) μg of SS1 per 10 μg of SS1S2 antigen, and PreS2 antigen activity per 10 μg of SS1S2 antigen corresponded to (7.0 ± 0.52) μg of SS2; SS1S2 antigen The sum of SS1 and SS2 antigen activities far exceeds 100%. Conclusions The co-expressed SS1S2 antigen has stronger immunogenicity than the SS1 antigen and SS2 antigen expressed separately. The activity of PreS1 and PreS2 antigen in co-expressed SS1S2 antigen is also enhanced.