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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 investigate and evaluate the immunogenicity of the recombinant Aβ1-15 epitope chimeric antigen 6Aβ15-T combined with different adjuvants that fused with helper T cell epitopes and to evaluate the immunogenicity of the recombinant chimeric antigen 6Aβ15-T as a marker of Alzheimer’s disease AD) vaccine feasibility. Methods Two groups of mice were immunized with recombinant 6Aβ15-T combined with aluminum adjuvant, Freund’s adjuvant and MF59 adjuvant respectively. Two control groups, Mock group and Mock group, (Control group), the immunogenicity of chimeric antigens was evaluated by specific antibodies and cellular immune responses. Results In BALB / c mice, all the three adjuvants significantly enhanced the chimeric antigen immune response and produced high levels of specific antibodies to Aβ (β-amyloid). In C57BL / 6 strain mice, the adjuvant enhanced the level of antibody produced by the chimeric antigen, but the non-adjuvanted group also produced a stronger antibody response. In both strains of mice, the immunized group of chimeric antigen produced mainly IgG1 subtype antibody responses, suggesting that the immune responses tended toward Th2 type, and the aluminum adjuvant group induced a higher level of IgG1 antibody whose IgG1 / IgG2a The ratio is also the largest. In addition, both chimeric mice produced only a cellular immune response to pan-DR helper T cell epitopes (PADRE) when chimeric antigen vaccines were administered with or without adjuvant, and none Aβ1-42 (Aβ42) specific cellular immune response. Conclusions The recombinant chimeric antigen 6Aβ15-T has good immunogenicity. In combination with different adjuvants, strong Th2-type Aβ-specific antibody responses are produced in both strains, and no obvious Aβ42-specific cellular immune responses are found As a candidate vaccine for AD, aluminum adjuvant is a more suitable adjuvant for this chimeric antigen 6Aβ15-T, which has good development prospect for human clinical trials in the future.