融合辅助性T细胞表位的重组Aβ 1-15表位嵌合抗原免疫原性研究  

Immunogenicity of a recombinant chimeric antigen using Aβ 1-15 epitope fused to a T helper epitope

作　　者：刘思[1,2] 赵萌[1,3] 许文惠[1] 余云舟[1] 王双[1] 俞炜源[1] 徐青[3] 孙志伟[1] 

机构地区：[1]军事医学科学院生物工程研究所,北京100071 [2]安徽大学生命科学学院,合肥236041 [3]北京交通大学生命科学与生物工程研究院,北京100044

出　　处：《军事医学》2014年第1期44-47,52,共5页Military Medical Sciences

基　　金：国家科技重大专项资助项目(2012ZX0901003-001-005);北京市自然科学基金资助项目(7122130);中央高校基本科研业务费专项资助项目(2012JBZ003)

摘　　要：目的探讨和评价融合辅助性T细胞表位的重组Aβ1-15表位嵌合抗原6Aβ15-T在联合不同佐剂时的免疫原性,以及重组嵌合抗原6Aβ15-T作为阿尔茨海默病(AD)疫苗的可行性。方法重组6Aβ15-T分别联合铝佐剂、弗氏佐剂、MF59佐剂,同时免疫两种品系小鼠,设置2个对照组即无佐剂嵌合抗原免疫组(Mock组)和未免疫组(Control组),通过特异性抗体和细胞免疫反应来评价嵌合抗原的免疫原性。结果在BALB/c品系小鼠实验中,3种佐剂均能明显地增强嵌合抗原的免疫反应,产生高水平针对Aβ(β-amyloid,β-淀粉样肽)的特异性抗体;在C57BL/6品系小鼠中,佐剂对嵌合抗原产生抗体水平有一定的增强作用,但无佐剂组也能产生较强的抗体反应。两种品系小鼠实验中,嵌合抗原免疫组主要产生IgG1亚型的抗体反应,提示免疫反应均趋向于Th2型,且铝佐剂组诱导产生更高水平的IgG1抗体,其IgG1/IgG2a的比值也最大。另外,嵌合抗原疫苗联合佐剂或无佐剂使用时,两种品系的小鼠仅产生了泛DR辅助T细胞表位(pan-DR helper T cell epitopes,PADRE)特异的细胞免疫反应,无Aβ1-42(简称Aβ42)特异性的细胞免疫反应。结论重组嵌合抗原6Aβ15-T具有良好的免疫原性,联合不同佐剂在两种品系小鼠均产生了较强Th2型Aβ特异性的抗体反应,无明显Aβ42特异性的细胞免疫反应,可作为AD的候选疫苗,并且铝佐剂是该嵌合抗原6Aβ15-T较合适的佐剂,对于今后应用于人体临床试验具有良好的开发前景。Objective To explore the immunogenicity of recombinant chimeric 6Aβ15-T including the Aβ1-15 epitope and a T-helper epitope formulated with different adjuvants and to evaluate its feasibility as a candidate vaccine for Alzheimer disease （AD）.Methods The recombinant chimeric antigen 6Aβ15-T formulated with Al adjuvant, Freund′s adjuvant or MF59 adjuvant was administered to two strains of mice .The 6Aβ15-T-immunized group without adjuvants （ Mock） and non-immunized group （Control） were included in this study as control groups .The specific antibody and cellular immune response of the chimeric antigen were evaluated .Results In BALB/c strain mice, three types of adjuvants could substan-tially boost the immunogenicity of chimeric antigen 6Aβ15-T and produce a high level of specific-Aβ（β-amyloid） antibod-ies.In C57BL/6 strain mice, the existence of adjuvants enhanced the immune response of 6Aβ15-T antigen, but the mice in Mock group also produced a strong antibody response .In two strains of mice, prevalence of anti-AβIgG1, which was an indicator of Th2 polarization, was observed in the 6Aβ15-T-immunized mice.Additionally, the Al adjuvant induced a high-er level of IgG1 antibody titers, and the ratio of IgG1/IgG2a was the largest.As expected, the 6Aβ15-T antigen formulated with or without adjuvants induced PADRE-specific, but not Aβ42-specific T cellular immune response .Conclusion The 6Aβ15-T antigens formulated with different types of adjuvants could induce strong Th 2-polarized Aβ42-specific antibody re-sponses without activating self-reactive Aβ42-specific T cells in two strains of mice .The results suggested that the recombi-nant chimeric antigen 6Aβ15-T is a good candidate vaccine for AD .

关 键 词：阿尔茨海默病 淀粉样Β蛋白 嵌合抗原 佐剂 免疫 表位 T淋巴细胞 

分 类 号：R392[医药卫生—免疫学]