Amyloid beta-HSP60 peptide conjugate vaccine treats a mouse model of Alzheimer's disease.

摘要

Active vaccination with amyloid beta peptide (A beta ) to induce beneficial antibodies was found to be effective in mouse models of Alzheimer's disease (AD), but human vaccination trials led to adverse effects, apparently caused by exuberant T-cell reactivity. Here, we sought to develop a safer active vaccine for AD with reduced T-cell activation. We treated a mouse model of AD carrying the HLA-DR DRB1*1501 allele, with the A beta B-cell epitope (A beta 1-15) conjugated to the self-HSP60 peptide p458. Immunization with the conjugate led to the induction of A beta -specific antibodies associated with a significant reduction of cerebral amyloid burden and of the accompanying inflammatory response in the brain; only a mild T-cell response specific to the HSP peptide but not to the A beta peptide was found. This type of vaccination, evoking a gradual increase in antibody titers accompanied by a mild T-cell response is likely due to the unique adjuvant and T-cell stimulating properties of the self-HSP peptide used in the conjugate and might provide a safer approach to effective AD vaccination.Digital Object Identifier http://dx.doi.org/10.1016/j.vaccine.2011.03.033