Active immunization of mice with an Aβ-Hsp70 vaccine

Abstract

Heat-shock proteins are highly immunogenic. Complexed with an antigen, they act as adjuvants, inducing a humoral and cellular immune response against both the antigen and the chaperone. In this study, we produced an Hsp70-supported vaccine to induce the generation of antibodies against amyloid-β (Aβ) peptides, the major constituent of β-amyloid plaques in Alzheimer's disease. The vaccine consisted of synthetic human Aβ42 covalently cross-linked with DnaK, an Hsp70 homolog of Escherichia coli. Active immunization of mice with this vaccine resulted in the generation of antibodies against Aβ, that were detectable in sera after the first booster immunization. Antibody titers varied markedly with the genetic background of the mice. Prophylactic short-term immunization of transgenic mice (APP tg2576) before the onset of plaques, however, did not prevent amyloid plaque deposition. There were no differences in the plaque load and in the level of Triton X-100-soluble Aβ peptides in the brains of immunized and control-treated transgenic mice. Unexpectedly, the level of formic-acid soluble Aβ peptides tended to be higher in immunized mice. The reason for the increase may be an enhanced deposition of Aβ in the small cerebral blood vessels. These data emphasize the need for anti-Aβ antibodies that remove Aβ peptides from the central nervous system without negative side effects. Copyright © 2004 S. Karger AG, Basel.