title: Alum and squalene-oil-in-water emulsion enhance the titer and avidity of anti-Aβ antibodies induced by multimeric protein antigen (1-11)E2, preserving the Igg1-skewed isotype distribution.
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 Aβ, while minimizing the risks of adverse reactions. Multimeric protein (1-11)E2 induces a robust and persistent antibody response to Aβ in mice, when formulated in Freund's adjuvant. The goal of this translational study was to evaluate the immunogenicity of (1-11)E2 formulated in alum (Alhydrogel 2%), or in a squalene oil-in-water emulsion (AddaVax), or without adjuvant. A IgG1-skewed isotype distribution was observed for the anti-Aβ antibodies generated in mice immunized with either the non-adjuvanted or the adjuvanted vaccine, indicating that (1-11)E2 induces a Th2-like response in all tested conditions. Both Alhydrogel 2% and AddaVax enhanced the titer and avidity of the anti-Aβ response elicited by (1-11)E2. We conclude that (1-11)E2 is a promising candidate for anti-Aβ immunization protocols that include alum or squalene-oil-in-water emulsion, or no adjuvant.
authors.affiliation: Institute of Genetics and Biophysics, CNR, Napoli, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mantile
authors.affiliation: Institute of Protein Biochemistry, CNR, Napoli, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Trovato
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Santoni
authors.affiliation: Institute of Genetics and Biophysics, CNR, Napoli, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Barba
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Ottonello
authors.affiliation: Institute of Protein Biochemistry, CNR, Napoli, Italy.
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: De Berardinis
authors.affiliation: Institute of Genetics and Biophysics, CNR, Napoli, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Prisco
mesh_terms: D000534:Alum Compounds / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000494:pharmacology; D004655:Emulsions / Q000494:pharmacology; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011136:Polysorbates / Q000494:pharmacology*; D013185:Squalene / Q000494:pharmacology*
chemical_list: C000590912:Addavax; D000534:Alum Compounds; D016229:Amyloid beta-Peptides; D000941:Antigens; D004655:Emulsions; D007074:Immunoglobulin G; D046912:Multiprotein Complexes; D010446:Peptide Fragments; D011136:Polysorbates; C115195:amyloid beta-protein (1-11); C041524:aluminum sulfate; D013185:Squalene