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目的:研究阿尔茨海默病β淀粉样肽(Aβ)B细胞表位疫苗2Aβ1-15-PADRE(Aβ-T)诱导产生抗体的免疫反应特性,并探讨不同佐剂对该疫苗免疫反应效果的影响。方法:合成了含2个Aβ42的B细胞表位—Aβ1-15及1个辅助T细胞表位—PADRE的多肽2Aβ1-15-PADRE。采用Al(OH)3佐剂,弗氏佐剂,Abisco佐剂,MF59佐剂分别与多肽疫苗联合免疫小鼠,并另设3个对照组:无佐剂多肽免疫组(Mock),PBS免疫组(PBS),未免疫组(Native)。结果:5组多肽免疫组小鼠均产生了针对Aβ的特异性抗体,无佐剂多肽免疫组的IgG抗体滴度最低,Al(OH)3佐剂组,MF59佐剂组,Abisco佐剂组小鼠IgG抗体滴度较高,弗氏佐剂组IgG抗体滴度最高。斑点杂交实验结果显示5组小鼠免疫后血清与Aβ42单体反应较弱,与寡聚体反应最明显,与纤维状Aβ42几乎不反应。结论:4种佐剂均能提高多肽疫苗的免疫反应,产生高水平抗Aβ的特异性抗体。5组免疫小鼠产生的抗体均与Aβ寡聚体反应较强,与纤维状Aβ42反应较弱,表明该多肽疫苗具有良好的应用前景。
OBJECTIVE: To study the immune response induced by the Aβ-B cell epitope vaccine Aβ-15-PADRE (Aβ-T) in Alzheimer’s disease and to investigate the effect of different adjuvants on the immunological response of the vaccine influences. Methods: Aβ1-15-PADRE, a B-cell epitope containing two Aβ42 and one peptide helper T cell epitope-PADRE, was synthesized. Mice were immunized with Al (OH) 3 adjuvant, Freund’s adjuvant, Abisco adjuvant and MF59 adjuvant in combination with peptide vaccine, respectively. Three control groups were also established: Mock, Group (PBS), non-immune group (Native). Results: The specific antibody against Aβ was produced in the immunized mice of all five groups. The IgG antibody titer of the immunized group was the lowest, while that of Al (OH) 3 adjuvant, MF59 adjuvant, Abisco adjuvant High titers of mouse IgG antibodies and IgG antibody titers of Freund’s adjuvant were the highest. The results of dot blot hybridization showed that the immune responses of the 5 groups of mice after immunization were weaker than that of Aβ42, the most obvious reaction with oligomer, and almost no reaction with fibrous Aβ42. CONCLUSION: All four adjuvants can increase the immune response of peptide vaccine and produce high-level anti-Aβ specific antibodies. Antibodies produced by the 5 groups of immunized mice reacted strongly with Aβ oligomer and reacted weakly with fibrillar Aβ42, indicating that the polypeptide vaccine has a good application prospect.