CAJ | 학술논문

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6 Aβ15-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C57 BL/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6 Aβ15-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6 Aβ15-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。
목적：탐토화평개융합보조성T세포표위적중조Aβ1-15표위감합항원6 Aβ15-T재연합불동좌제시적면역원성，이급중조감합항원6Aβ15-T작위아이자해묵병（ AD）역묘적가행성。방법중조6Aβ15-T분별연합려좌제、불씨좌제、MF59좌제，동시면역량충품계소서，설치2개대조조즉무좌제감합항원면역조（ Mock조）화미면역조（ Control조），통과특이성항체화세포면역반응래평개감합항원적면역원성。결과재BALB/c품계소서실험중，3충좌제균능명현지증강감합항원적면역반응，산생고수평침대Aβ（β-amyloid，β-정분양태）적특이성항체；재C57 BL/6품계소서중，좌제대감합항원산생항체수평유일정적증강작용，단무좌제조야능산생교강적항체반응。량충품계소서실험중，감합항원면역조주요산생IgG1아형적항체반응，제시면역반응균추향우Th2형，차려좌제조유도산생경고수평적IgG1항체，기IgG1/IgG2a적비치야최대。령외，감합항원역묘연합좌제혹무좌제사용시，량충품계적소서부산생료범DR보조T세포표위（ pan-DR helper T cell epitopes ，PADRE）특이적세포면역반응，무Aβ1-42（간칭Aβ42）특이성적세포면역반응。결론중조감합항원6 Aβ15-T구유량호적면역원성，연합불동좌제재량충품계소서균산생료교강Th2형Aβ특이성적항체반응，무명현Aβ42특이성적세포면역반응，가작위AD적후선역묘，병차려좌제시해감합항원6 Aβ15-T교합괄적좌제，대우금후응용우인체림상시험구유량호적개발전경。
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 .