阿尔茨海默病多肽表位疫苗免疫原性研究

目的以淀粉样蛋白Aβ作为免疫靶标,优化阿尔茨海默病多肽B细胞表位疫苗。方法化学合成人Aβ1-42多肽、含B细胞表位的Aβ1-15多肽、含两个B细胞表位及一个辅助T细胞表位PADRE的多肽Aβ（1-15）2-PADRE及含13个氨基酸的PADRE。以上4种多肽免疫普通BALB/c小鼠,ELISA试验比较免疫后的小鼠血清抗体水平和亚型,点杂交分析其与不同状态Aβ的结合免疫特性。结果 Aβ（1-15）2-PADRE组免疫后诱导产生了良好的免疫效果,100μg组4次免疫后其抗体滴度可以达到1∶3500;抗体亚型分析后得知,其主要产生IgG1型抗体,免疫反应完全偏向于Th2型,其免疫血清可与不同状态Aβ的结合免疫特性不同。结论辅助T细胞表位PADRE增强了B细胞表位Aβ1-15的免疫效果,并且其免疫血清抗体与Aβ寡聚体结合效果更好。

Immunogenicity of polypeptide epitope vaccine against Alzheimer's disease

Objective To optimize the B cell epitope vaccine of Aβ against Alzheimer′s disease.Methods The polypeptides of Aβ1-42,the Aβ（1-15）2-PADRE having two B cell epitopes of Aβ and an universal T helper epitopes-PADRE and the PADRE having 13 amino acid were synthesized.The immunogenicity of four peptides was evaluated in the BALB/c mouse model by ELISA.Results After the fourth immunization,high antibody titers were detected up to 1∶3500 in the Aβ（1-15）2-PADRE group and the isotope was mainly IgG1.Immune responses induced by the peptide were absolutely prone to Th2 phenotype.The sera antibodies could differently bind monomer,oligomer and fiber form of Aβ by dot blot.Conclusion The anti-amyloid-β antibody production could be enhanced by the universal T cell epitopes and polarize the immune response towards a Th2 phenotype.The sera antibodies could bind better with oligomer than with other forms of Aβ.