Vaccination with (1-11)E2 in alum efficiently induces an antibody response to β-amyloid without affecting brain β-amyloid load and microglia activation in 3xTg mice.

Abstract

Immunization against β-amyloid (Aβ) is pursued as a possible strategy for the prevention of Alzheimer's disease (AD). In clinical trials, Aβ 1-42 proved poorly immunogenic and caused severe adverse effects; therefore, safer and more immunogenic candidate vaccines are needed. Multimeric protein (1-11)E2 is able to induce an antibody response to Aβ, immunological memory, and IL-4 production, with no concomitant anti-Aβ T cell response. Antisera recognize Aβ oligomers, protofibrils, and fibrils. In this study, we evaluated the effect of prophylactic immunization with three doses of (1-11)E2 in alum in the 3xTg mouse model of AD. Immunization with (1-11)E2 efficiently induced anti-Aβ antibodies, but afforded no protection against Aβ accumulation and neuroinflammation. The identification of the features of the anti-Aβ immune response that correlate with the ability to prevent Aβ accumulation remains an open problem that deserves further investigation.