Immune shaping and the development of Alzheimer's disease vaccines

Given the emotional, social, and financial devastation wrought by Alzheimer's disease (AD), it is imperative that effective therapeutics be devised to ameliorate this presently incurable disorder. Vaccine-based approaches have been developed to target and eliminate amyloid beta (Abeta), a key peptide implicated in AD pathogenesis. Preclinical successes in AD mouse models created excitement and impetus for the clinical application of an Abeta-based vaccine. Eliciting immune responses against a self-peptide (that is, a peptide produced by the organism itself), such as Abeta, carries with it the potential to induce autoimmune and inflammatory conditions in the vaccinated individual, a caveat borne out in multiple patients enrolled as part of a recent clinical trial. These clinical adverse events seemingly overshadowed interesting behavioral stabilization and alterations of Abeta burden in these and other vaccinated patients, thus speaking to the potential of immunotherapy for AD. Understanding the mechanisms by which vaccines reduce Abeta burden in AD brain and the types of immune responses raised, as well as developing new modalities of vaccine delivery that facilitate the modulation of elicited immune responses, will undoubtedly lead to a new generation of efficacious Abeta immunotherapeutics with improved safety profiles.