title: A comparative evaluation of a novel vaccine in APP/PS1 mouse models of Alzheimer's disease.
abstract: Immunization against amyloid-beta-peptide (Aβ) has been widely investigated as a potential immunotherapeutic approach for Alzheimer's disease (AD). With the aim of developing an active immunogenic vaccine without need of coadjuvant modification for human trials and therefore avoiding such side effects, we designed the Aβ 1-42 vaccine (EB101), delivered in a liposomal matrix, that based on our previous studies significantly prevents and reverses the AD neuropathology, clearing Aβ plaques while markedly reducing neuronal degeneration, behavioral deficits, and minimizing neuroinflammation in APP/PS1 transgenic mice. Here, the efficacy of our immunogenic vaccine EB101 was compared with the original immunization vaccine cocktail Aβ 42 + CFA/IFA (Freund's adjuvant), in order to characterize the effect of sphingosine-1-phosphate (S1P) in the immunotherapeutic response. Quantitative analysis of amyloid burden showed a notable decrease in the neuroinflammation reaction against Aβ plaques when S1P was compared with other treatments, suggesting that S1P plays a key role as a neuroprotective agent. Moreover, EB101 immunized mice presented a protective immunogenic reaction resulting in the increase of Aβ-specific antibody response and decrease of reactive glia in the affected brain areas, leading to a Th2 immunological reaction.
authors.affiliation: Department of Neuroscience, EuroEspes Biotechnology, Poligono de Bergondo, Nave F, 15165 A Coruña, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Carrera
authors.affiliation: Department of Neuroscience, EuroEspes Biotechnology, Poligono de Bergondo, Nave F, 15165 A Coruña, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Etcheverría
authors.affiliation: Department of Neuroscience, EuroEspes Biotechnology, Poligono de Bergondo, Nave F, 15165 A Coruña, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Fernández-Novoa
authors.affiliation: Department of Neuroscience, EuroEspes Biotechnology, Poligono de Bergondo, Nave F, 15165 A Coruña, Spain.
authors.forename: Valter Ruggero Maria
authors.initials: VR
authors.lastname: Lombardi
authors.affiliation: Department of Neurobiology, Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port Saint Lucie, FL 34987, USA.
authors.forename: Madepalli Krishnappa
authors.initials: MK
authors.lastname: Lakshmana
authors.affiliation: EuroEspes Biomedical Research Center, Institute for CNS Disorders and Chair of Genomic Medicine, University of Camilo Jose Cela, 15165 Madrid, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Cacabelos
authors.affiliation: Atlas Pharmaceuticals, Sunnyvale, CA 94089, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Vigo
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology; D016564:Amyloid beta-Protein Precursor / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D001921:Brain / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007114:Immunization / Q000379:methods; D008246:Lysophospholipids / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D058225:Plaque, Amyloid / Q000276:immunology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000276:immunology; D014611:Vaccination / Q000379:methods; D014612:Vaccines / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D008246:Lysophospholipids; D009842:Oligopeptides; C449186:PS1 antigen; D010446:Peptide Fragments; D014612:Vaccines; C060506:sphingosine 1-phosphate; D013110:Sphingosine