摘要
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 compare the immunogenicity and antigenic activities of co-expressed hepatitis B surface antigen（HBsAg）containing PreS1 and PreS2 epitopes with those of mixture of HBsAg containing PreS1 epitope（SS1）and that containing PreS2（SS2）,and provide a basis for selection of formula of HB vaccine. Methods SS1S2 and SS1 ＋ SS2（1 ∶ 1 mixture）antigens were adsorbed with aluminium hydroxide to prepare two HB vaccines respectively,in which both the total antigen contents were 20 μg / ml. BALB / c mice were injected i. p. once with the vaccines at dosages of 1. 0,0. 25 and 0. 06 μg,of which the blood samples were collected 1,2 and 4 weeks later,and determined for serum antibodies against HBV S,PresS1 and PreS2 by ELISA. The SS1 or SS2 antigen contents in six batches of SS1S2 antigen were determined by ELISA using purified SS1 or SS2 antigen as a reference. Results The positive conversion rates of anti-S induced by SS1S2 vaccine at three dosages 1,2 and 4 weeks after immunization were significantly higher than those by SS1 ＋ SS2 vaccine at the corresponding dosages,while those of anti-PreS1 by 0. 25 μg SS1S2 vaccine than those by SS1 ＋ SS2 vaccine at the corresponding dosages. The positive conversion rates of anti-PreS2 induced by SS1S2vaccine at three dosages were similar to those by SS1 ＋ SS2 vaccine 1 and 2 weeks after immunization. However,the positive conversion rates of anti-PreS2 induced by 1. 0 and 0. 25 μg SS1S2 4 weeks after immunization were higher than those by SS1 ＋ SS2 vaccine. The GMTs of anti-S and anti-PreS1 induced by SS1S2 vaccine at three dosages 4 weeks after immunization were higher than those by SS1 ＋ SS2 vaccine at the corresponding dosages. The GMTs of anti-PreS2induced by 1. 0 and 0. 25 μg SS1S2 vaccine were higher than those by SS1 ＋ SS2 vaccine at the corresponding dosages.The determination results of six batches of SS1S2 antigen showed that the PreS1 activity in each 10 μg SS1S2 antigen was equivalent to that in（12. 1 ± 0. 84）μg SS1,while the PreS2 antigen activity was equivalent to that in（7. 0 ± 0. 52）μg SS2. The sum of SS1 and SS2 activities in SS1S2 antigen was far more than 100%. Conclusion The co-expressed SS1S2 antigen is more immunogenic than SS1 and SS2 antigens expressed alone,in which the PreS1 and PreS2 antigenic activities are enhanced.
出处
《中国生物制品学杂志》
CAS
CSCD
2014年第7期873-877,共5页
Chinese Journal of Biologicals
关键词
前S表位
乙肝疫苗
免疫原性
抗原活性
PreS epitope Hepatitis B vaccine Immunogenicity Antigenic activity
