title: The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid β Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs.
abstract: The reduction of brain amyloid beta (Aβ) peptides by anti-Aβ antibodies is one of the possible therapies for Alzheimer's disease. We previously reported that the Aβ peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-Aβ antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβ antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ 40, and Aβ 42 compared to Aβ fibrils. The levels of serum anti-Aβ antibodies and plasma Aβ peptides increased in both animals and decreased the brain Aβ 40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβ antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβ peptides and their toxic effects via clearance of Aβ peptides by generated antibodies.
authors.affiliation: Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yano
authors.affiliation: Venture Science Laboratories, R&D Division, Daiichi-Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Ito
authors.affiliation: Quality Assurance Division, Hayashibara Co., Ltd., 675-1 Fujisaki, Naka-ku, Okayama 702-8006, Japan.
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Miwa
authors.affiliation: R&D Planning Department, R&D Division, Daiichi-Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kanazawa
authors.affiliation: Development Oversight Function, R&D Division, Daiichi-Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Chiba
authors.affiliation: Biological Research Department, Drug Discovery and Biomedical Technology Unit, Daiichi-Sankyo R&D Novare Co., Ltd., 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Iigo
authors.affiliation: Biological Research Department, Drug Discovery and Biomedical Technology Unit, Daiichi-Sankyo R&D Novare Co., Ltd., 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kashimoto
authors.affiliation: Biological Research Laboratories, R&D Division, Daiichi-Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kanda
authors.affiliation: Biological Research Laboratories, R&D Division, Daiichi-Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Murata
authors.affiliation: Venture Science Laboratories, R&D Division, Daiichi-Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Makino
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D022422:Diphtheria-Tetanus Vaccine / Q000276:immunology*; D006168:Guinea Pigs; D006801:Humans; D007114:Immunization; D008252:Macaca fascicularis; D013997:Time Factors; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies; D016207:Cytokines; D022422:Diphtheria-Tetanus Vaccine; D022223:Vaccines, Subunit