Rationale for Peptide and DNA Based Epitope Vaccines for Alzheimer's Disease Immunotherapy

Amyloid-beta (A beta) immunotherapy has received considerable attention as a promising approach for reducing the level of A beta in the CNS of Alzheimer's disease patients. However, the first Phase II clinical trial, for the immune therapy AN1792, was halted when a subset of those immunized with A beta(42) developed adverse events in the central nervous system. In addition, data from the trial indicated that there was a low percentage of responders and generally low to moderate titers in the patients that received the vaccine. Generated antibodies reduced beta-amyloid deposits in the parenchyma of patients' brains, but no reduction in soluble A beta or significant improvements in cognitive function of patients were observed. These data and data from pre-clinical studies suggest that reduction in the most toxic oligomeric forms of A beta is important for prevention or slowing down of the progression of cognitive decline, and that vaccination should be started prior to irreversible accumulation of the oligomeric A beta, at the early stages of AD. Protective immunotherapy requires a development of safe and effective strategy for A beta immunotherapy. In this review, the rationale for developing epitope vaccines for the treatment of AD will be discussed. We believe that an epitope vaccine will induce an adequate anti-A beta antibody response in the absence of potentially adverse self T cell-mediated events, making it possible to start immunization at the early stages of AD.