A Comparative Evaluation of a Novel Vaccine in APP/PS1 Mouse Models of Alzheimer's Disease

作者：Carrera Ivan^*; Etcheverria Ignacio; Fernandez Novoa Lucia; Maria Lombardi Valter Ruggero; Lakshmana Madepalli Krishnappa; Cacabelos Ramon; Vigo Carmen

来源：Biomed Research International, 2015, 2015: 807146.

DOI：10.1155/2015/807146

Immunization against amyloid-beta-peptide (A beta) has been widely investigated as a potential immunotherapeutic approach for Alzheimer's disease (AD). With the aim of developing an active immunogenic vaccine without need of coadjuvant modification for human trials and therefore avoiding such side effects, we designed the A beta(1-42) vaccine (EB101), delivered in a liposomal matrix, that based on our previous studies significantly prevents and reverses the AD neuropathology, clearing A beta plaques while markedly reducing neuronal degeneration, behavioral deficits, and minimizing neuroinflammation in APP/PS1 transgenic mice. Here, the efficacy of our immunogenic vaccine EB101 was compared with the original immunization vaccine cocktail A beta(42) + CFA/IFA (Freund's adjuvant), in order to characterize the effect of sphingosine-1-phosphate (S1P) in the immunotherapeutic response. Quantitative analysis of amyloid burden showed a notable decrease in the neuroinflammation reaction against A beta plaques when S1P was compared with other treatments, suggesting that S1P plays a key role as a neuroprotective agent. Moreover, EB101 immunized mice presented a protective immunogenic reaction resulting in the increase of A beta-specific antibody response and decrease of reactive glia in the affected brain areas, leading to a Th2 immunological reaction.

• 出版日期2015