title: Prophylactic Vaccine Based on Pyroglutamate-3 Amyloid β Generates Strong Antibody Response and Rescues Cognitive Decline in Alzheimer's Disease Model Mice.
abstract: Clearance of amyloid β (Aβ) by immunotherapy is one of the fancy methods to treat Alzheimer's disease (AD). However, the failure of some clinical trials suggested that there may be something ignored in the past development of immunotherapy. Pyroglutamate-3 Aβ (AβpE3-X), which was found to be abundant in the patients' brain, has attracted much attention after the report that AβpE3-42could serve as a template to exacerbate the aggregation of Aβ. In addition, AβpE3-Xcould not be recognized by the antibodies targeting the N-terminus of Aβ, suggesting that AβpE3-Xmaybe the ignored one. Indeed, passive immunization targeting AβpE3-Xhas shown some beneficial results, while active immunotherapy has not been extensively studied. In the present study, we designed and synthesized a novel peptide vaccine targeting AβpE3-X, which contains AβpE3-15as B cell epitope and P2 as T cell epitope. We showed that this vaccine could induce strong antibody response to AβpE3-X. We also showed that prophylactic immunization of AD model mice with our vaccine could reduce Aβ plaques and rescue cognitive decline. This new kind of Aβ vaccine will open up new directions for AD immunotherapy.
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.
authors.forename: Gao
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.
authors.forename: Zhi-Wen
authors.initials: ZW
authors.lastname: Hu
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.
authors.forename: Pu-Guang
authors.initials: PG
authors.lastname: Chen
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.
authors.forename: Zhan-Yi
authors.initials: ZY
authors.lastname: Sun
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Chen
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.|Beijing Institute for Brain Disorders , Beijing 100069, China.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D023582:Alzheimer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D058227:Amyloidogenic Proteins / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000097:blood; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology* / Q000627:therapeutic use*; D058225:Plaque, Amyloid / Q000188:drug therapy; D053764:Presenilin-1 / Q000235:genetics; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D058227:Amyloidogenic Proteins; D000906:Antibodies; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C532271:amyloid beta-protein (3-42), pyroglutamyl(3)-
keywords: Alzheimer’s disease (AD); Aβ plaques; prophylactic immunization; pyroglutamate-3 Aβ; vaccine