Abstract: The objective of this study is to obtain a mimotope vaccine specifically targeting to pathogenic Aβ42 oligomer. In previous studies，we purified an antibody IVIG-AOB，which specifically recognizes Aβ42 oligomers，from intravenous immunoglobulin（IVIG）by affinity chromatography. Using phage display technique，a series of ring-shape mimotope polypeptides were screened for specific binding to IVIG-AOB. These oligomer epitope peptide genes were then cloned to HBc-VLP vector and the recombinant proteins were expressed in Escherichia coli. After that，the recombinant Aβ42 oligomer conformational epitope HBc-VLP vaccine were applied to Balb/c mice. The antibody responses induced by the Aβ42 oligomer-targeted VLP vaccine were determined. Five mimotope polypeptides specifically-bound with IVIG-AOB were successfully screened from phage cyclic peptide library and cloned into HBc-VLP vector. The recombinant proteins were successfully expressed in E. coli. HBc-C4 elicited the highest antibody titer after vaccination to Balb/c mice. Conclusively，Aβ oligomer is the major factor in the pathological processes of Alzheimer’s disease（AD）. The mimotope HPc-VLP vaccine based on the unique structure of Aβ42 oligomer induced body to generate the antibody targeting and neutralizing the toxic Aβ42 oligomers，while not affecting its normal physiological function，thus it plays a fundamental role in the treatment of AD.

Key words: Alzheimer’s disease, Aβ42 oligomers, mimotope, vaccine, antibody