Abstract
Six recombinant proteins GST-Aβ28/Aβ35/Aβ42 and GST-I-Aβ28/Aβ35/Aβ42 [I was the abbreviation for an immunostimulatory sequence that consisted of pan HLA DR binding epitope (PADRE) and Tetanus toxin epitope (TT)] were used as antigens after expressed and purified to immunize mice. The strongest antibody response against Aβ42 (titer 1:3200) was achieved by GST-I-Aβ28 or GST-Aβ42 immunization. However, IgG1 and IgG2b were the predominant serum antibody isotype responses by GST-I-Aβ28 immunization, whereas did IgG2a by GST-Aβ42 immunization. Thus, it indicated that GST-I-Aβ28 immunization in a mouse mainly evoked a stronger Th-2-type response; whereas, GST-Aβ42 immunization mainly elicited a Th-1-type response. Moreover, GST-I-Aβ28-induced serum antibodies had higher specificity to Aβ42 monomers and oligomers than to protofibrils and mature fibrils and exhibited the highest efficacy to block Aβ42 aggregation or fibrillogenesis and to disassemble Aβ42 aggregates in vitro. GST-I-Aβ28-induced serum antibodies also showed the most protective and restorative effects on target cells in vitro by inhibiting or neutralizing Aβ42-induced cytotoxicity. All of the above results indicated that Aβ28 could be speculated to substitute for Aβ42 and would become a better antigenic peptide for Alzheimer's disease immunotherapy in the presence of additional Th-cell epitopes such as the immunostimulatory sequence (I) applied in this study.
Published Version
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