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.

Keywords:
Alzheimer’s disease, Vaccination, Immunization, DnaK, Heat-shock proteins, Chaperone, Adjuvant
This content is only available via PDF.
© 2004 S. Karger AG, Basel
2004
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.