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

PLoS One. 2014 Jul 1;9(7):e101474. doi: 10.1371/journal.pone.0101474. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alum Compounds / pharmacology*
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / immunology
  • Alzheimer Disease* / therapy
  • Amyloid beta-Peptides* / pharmacology
  • Animals
  • Antigens* / pharmacology
  • Emulsions / pharmacology
  • Female
  • Immunoglobulin G / immunology*
  • Mice
  • Mice, Transgenic
  • Multiprotein Complexes* / pharmacology
  • Peptide Fragments* / pharmacology
  • Polysorbates / pharmacology*
  • Squalene / pharmacology*

Substances

  • Addavax
  • Alum Compounds
  • Amyloid beta-Peptides
  • Antigens
  • Emulsions
  • Immunoglobulin G
  • Multiprotein Complexes
  • Peptide Fragments
  • Polysorbates
  • amyloid beta-protein (1-11)
  • aluminum sulfate
  • Squalene