Recombinant GST-I-A beta 28-induced efficient serum antibody against A beta 42.
Six recombinant proteins GST-A beta 28/A beta 35/A beta 42 and GST-I-A beta 28/A beta 35/A beta 42 [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 A beta 42 (titer 1:3200) was achieved by GST-I-A beta 28 or GST-A beta 42 immunization. However, IgG1 and IgG2b were the predominant serum antibody isotype responses by GST-I-A beta 28 immunization, whereas did IgG2a by GST-A beta 42 immunization. Thus, it indicated that GST-I-A beta 28 immunization in a mouse mainly evoked a stronger Th-2-type response; whereas, GST-A beta 42 immunization mainly elicited a Th-1-type response. Moreover, GST-I-A beta 28-induced serum antibodies had higher specificity to A beta 42 monomers and oligomers than to protofibrils and mature fibrils and exhibited the highest efficacy to block A beta 42 aggregation or fibrillogenesis and to disassemble A beta 42 aggregates in vitro. GST-I-A beta 28-induced serum antibodies also showed the most protective and restorative effects on target cells in vitro by inhibiting or neutralizing A beta 42-induced cytotoxicity. All of the above results indicated that A beta 28 could be speculated to substitute for A beta 42 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.
Huang
Xuemei
X
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, 2519 Jie-Fang Road, Changchun 130021, PR China.
Wang
Jiapeng
J
Cui
Lili
L
Zou
Xiaohuan
X
Zhang
Yingjiu
Y
D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000097:blood; D000939:Epitopes / Q000276:immunology; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D058225:Plaque, Amyloid / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D016229:Amyloid beta-Peptides; D000906:Antibodies; D000939:Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C075222:amyloid beta-protein (1-42)