Active immunization with the peptide epitope vaccine Aβ3-10-KLH induces a Th2-polarized anti-Aβ antibody response and decreases amyloid plaques in APP/PS1 transgenic mice.
Active amyloid-β (Aβ) immunotherapy is effective in preventing Aβ deposition, facilitating plaque clearance, and improving cognitive functions in mouse models of Alzheimer's disease (AD). Developing a safe and effective AD vaccine requires a delicate balance between inducing adequate humoral immune responses and avoiding T cell-mediated autoimmune responses. In this study, we designed 2 peptide epitope vaccines, Aβ3-10-KLH and 5Aβ3-10, prepared respectively by coupling Aβ3-10 to the immunogenic carrier protein keyhole limpet hemocyanin (KLH) or by joining 5 Aβ3-10 epitopes linearly in tandem. Young APP/PS1 mice were immunized subcutaneously with Aβ3-10-KLH or 5Aβ3-10 mixed with Freund's adjuvant, and the immunopotencies of these Aβ3-10 peptide vaccines were tested. Aβ3-10-KLH elicited a robust Th2-polarized anti-Aβ antibody response and inhibited Aβ deposition in APP/PS1 mice. However, 5Aβ3-10 did not induce an effective humoral immune response. These results indicated that Aβ3-10-KLH may be a safe and efficient vaccine for AD and that conjugating the antigen to a carrier protein may be more effective than linking multiple peptide antigens in tandem in applications for antibody production and vaccine preparation.
Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China. Electronic address: dingding8766@163.com.
Li
L
Ding
Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
Yuan
Y
Meng
Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
Hui-Yi
HY
Zhang
Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
Wen-Chao
WC
Yin
Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
Yi
Y
Yan
Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China. Electronic address: cypcmu@163.com.
Yun-Peng
YP
Cao
D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D023582:Alzheimer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000276:immunology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D000906:Antibodies / Q000097:blood*; D001921:Brain / Q000473:pathology; D000939:Epitopes; D007074:Immunoglobulin G / Q000097:blood; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology; D058225:Plaque, Amyloid / Q000473:pathology*; D053764:Presenilin-1 / Q000235:genetics*; D018418:Th2 Cells / Q000276:immunology*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D000939:Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; D053764:Presenilin-1; D022223:Vaccines, Subunit; C580804:presenilin 1, mouse
Alzheimer's disease; Amyloid-β peptide; Carrier protein; Epitope vaccine; Multiple-antigen peptides