Active immunization of mice with an Abeta-Hsp70 vaccine.
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-beta (Abeta) peptides, the major constituent of beta-amyloid plaques in Alzheimer's disease. The vaccine consisted of synthetic human Abeta42 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 Abeta, 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 Abeta peptides in the brains of immunized and control-treated transgenic mice. Unexpectedly, the level of formic-acid soluble Abeta peptides tended to be higher in immunized mice. The reason for the increase may be an enhanced deposition of Abeta in the small cerebral blood vessels. These data emphasize the need for anti-Abeta antibodies that remove Abeta peptides from the central nervous system without negative side effects.
Koller
Michael F
MF
Institute of Biochemistry, Division of Psychiatry Research, University of Zürich, Zürich, Switzerland. miko@bioc.unizh.ch
Mohajeri
M Hasan
MH
Huber
Michael
M
Wollmer
M Axel
MA
Roth Z'graggen
Birgit V
BV
Sandmeier
Erika
E
Moritz
Eva
E
Tracy
Jay
J
Nitsch
Roger M
RM
Christen
Philipp
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000276:immunology / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000097:blood; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000187:drug effects / Q000473:pathology; D014611:Vaccination
D000276:Adjuvants, Immunologic; D016229:Amyloid beta-Peptides; D000906:Antibodies; D018840:HSP70 Heat-Shock Proteins