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

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.