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

The development of active immunotherapy for Alzheimer's disease (AD) requires the identification of immunogens that can ensure a high titer antibody response toward A beta, while minimizing the risks of adverse reactions. Multimeric protein (1-11)E2 induces a robust and persistent antibody response to A beta 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-A beta 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-A beta response elicited by (1-11)E2. We conclude that (1-11)E2 is a promising candidate for anti-A beta immunization protocols that include alum or squalene-oil-in-water emulsion, or no adjuvant.