Development of Alzheimer’s Disease Vaccines: a Perspective

Like infectious disease vaccines, effective Alzheimer’s disease vaccines should elicit an antibody response similar to the natural autoantibodies found in serum and preparations of intravenous immunoglobulins, which recognize an array of amyloid-β conformations. An immune response that is the result of a progressive formation over time of antibodies against toxic amyloid-β conformations and that different from most vaccines under development, would require the whole protein as an antigen, including both B and T-cell epitopes. However, due to the presence of amyloid-β T-cell epitopes and the fact that such a protein is a Th1 immune modulator, safe and effective vaccines, besides eliciting Th2 immunity, should inhibit but not abolish Th1 immunity, which is needed for protection against pathogens; a strategy that would apply to other potential Alzheimer’s disease vaccine antigens, e.g. tau. Due to immunosenescence, these vaccines would be more effective for preventive rather than therapeutic purposes, as younger individuals produce a better immune response. Recently developed novel adjuvants that most probably act at the dendritic cell level and that can deliver such a selective Th2 immune modulation while inhibiting Th1 immunity, would be crucial for the development of these proposed vaccines.