title: A multimeric immunogen for the induction of immune memory to beta-amyloid.
abstract: The development of active immunotherapy for Alzheimer's disease (AD) requires the identification of immunogens that can ensure a high titer antibody response toward beta-amyloid, whereas minimizing the risks of a cell-mediated adverse reaction. We describe here two novel anti-beta-amyloid vaccines that consist of 'virus like particles' formed by a domain of the bacterial protein E2 that is able to self-assemble into a 60-mer peptide. Peptides 1-11 and 2-6 of beta-amyloid were displayed as N terminal fusions on the surface of the E2 particles. E2-based vaccines induced a fast-rising, robust and persistent antibody response to beta-amyloid in all vaccinated mice. The immune memory induced by a single administration of vaccine (1-11) E2 can be rapidly mobilized by a single booster injection, leading to a very high serum concentration of anti-beta-amyloid antibodies (above 1 mg ml(-1)). E2 vaccination polarizes the immune response toward the production of the anti-inflammatory cytokine interleukin-4 and does not induce a T cell response to beta-amyloid. Thus, E2-based vaccines are promising candidates for the development of immunotherapy protocols for AD.
authors.affiliation: Istituto di Genetica e Biofisica ABT, CNR, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mantile
authors.forename: Carla
authors.initials: C
authors.lastname: Basile
authors.forename: Valeria
authors.initials: V
authors.lastname: Cicatiello
authors.forename: Diana
authors.initials: D
authors.lastname: De Falco
authors.forename: Antonella
authors.initials: A
authors.lastname: Caivano
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: De Berardinis
authors.forename: Antonella
authors.initials: A
authors.lastname: Prisco
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014614:Vaccines, Synthetic / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D058425:Vaccines, Virus-Like Particle; D015847:Interleukin-4; D007371:Interferon-gamma