Dendrimeric A beta 1-15 is an effective immunogen in wildtype and APP-tg mice

Immunization of humans and APP-tg mice with full-length beta -amyloid (A beta ) results in reduced cerebral A beta levels. However, due to adverse events in the AN1792 trial, alternative vaccines are required. We investigated dendrimeric A beta 1-15 (dA beta 1-15), which is composed of 16 copies of A beta 1-15 peptide on a branched lysine core and thus, includes an A beta -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-A beta antibody production. Antibody isotypes were mainly IgG1 for subcutaneous or transcutaneous immunization and IgG2b for intranasal immunization, suggestive of a Th2-biased response. All A beta antibodies preferentially recognized an epitope in A beta 1-7. 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 A beta peptide was minimal indicating the lack of an A beta -specific cellular immune response. Anti-A beta antibodies bound monomeric, oligomeric, and fibrillar A beta . Our data suggest that dA beta 1-15 may be an effective and potentially safer immunogen for Alzheimer's disease (AD) vaccination.