Dendrimeric Aβ1–15 is an effective immunogen in wildtype and APP-tg mice

Immunization of humans and APP-tg mice with full-length β-amyloid (Aβ) results in reduced cerebral Aβ levels. However, due to adverse events in the AN1792 trial, alternative vaccines are required. We investigated dendrimeric Aβ1–15 (dAβ1–15), which is composed of 16 copies of Aβ1–15 peptide on a branched lysine core and thus, includes an Aβ-specific B cell epitope but lacks the reported T cell epitope. Immunization by subcutaneous, transcutaneous, and intranasal routes of B6D2F1 wildtype mice led to anti-Aβ antibody production. Antibody isotypes were mainly IgG1 for subcutaneous or transcutaneous immunization and IgG2b for intranasal immunization, suggestive of a Th2-biased response. All Aβ antibodies preferentially recognized an epitope in Aβ1–7. Intranasal immunization of J20 APP-tg mice resulted in a robust humoral immune response with a corresponding significant reduction in cerebral plaque burden. Splenocyte proliferation against Aβ peptide was minimal indicating the lack of an Aβ-specific cellular immune response. Anti-Aβ antibodies bound monomeric, oligomeric, and fibrillar Aβ. Our data suggest that dAβ1–15 may be an effective and potentially safer immunogen for Alzheimer's disease (AD) vaccination.