A fresh perspective from immunologists and vaccine researchers: active vaccination strategies to prevent and reverse Alzheimer's disease.

Traditional vaccination against infectious diseases relies on generation of cellular and humoral immune responses that act to protect the host from overt disease even though they do not induce sterilizing immunity. More recently, attempts have been made with mixed success to generate therapeutic vaccines against a wide range of noninfectious diseases including neurodegenerative disorders. After the exciting first report of successful vaccine prevention of progression of an Alzheimer's disease (AD) animal model in 1999, various epitope-based vaccines targeting amyloid beta (Aβ) have proceeded to human clinical trials, with varied results. More recently, AD vaccines based on tau protein have advanced into clinical testing too. This review seeks to put perspective to the mixed results obtained so far in clinical trials of AD vaccines and discusses the many pitfalls and misconceptions encountered on the path to a successful AD vaccine, including better standardization of immunologic efficacy measures of antibodies, immunogenicity of platform/carrier and adjuvants.