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

Amyloid-beta (Aβ) immunotherapy has received considerable attention as a promising approach for reducing the level of Aβ 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 Aβ42 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 β-amyloid deposits in the parenchyma of patients' brains, but no reduction in soluble Aβ 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 Aβ 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 Aβ, at the early stages of AD. Protective immunotherapy requires a development of safe and effective strategy for Aβ 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-Aβ 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.