Document Detail


Virus-like peptide vaccines against Abeta N-terminal or C-terminal domains reduce amyloid deposition in APP transgenic mice without addition of adjuvant.
MedLine Citation:
PMID:  20066498     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Immunotherapy against the Abeta peptide is increasingly viewed as an effective means of preventing and even decreasing Abeta deposition in transgenic mouse models and human cases of Alzheimer's disease. A prior active immunization trial was halted due to adverse events which occurred subsequent to a change in the adjuvant used in the vaccine preparation. Although widely used in experimental studies, adjuvants available for use in vaccines intended for humans are limited. We compared two vaccine preparations in which an immunogenic bacteriophage was conjugated with either an N-terminal (Abeta1-9) or C-terminal (Abeta28-40) peptide sequence from the Abeta molecule. We found that both produced significant antibody titers without use of additional adjuvants. Surprisingly, the response to the N terminal sequence was comprised largely of a stable IgM response, while the C-terminal vaccine produced an IgG response with minimal IgM reactivity. Both of these immunogens reduced Abeta levels when tissues were examined 8 months after the first inoculation. These data demonstrate that (a) C-terminal specific vaccines can effectively lower Abeta and (b) IgM antibodies against Abeta may be capable of lowering Abeta, possibly through action in the brain rather than the periphery.
Authors:
Qing-you Li; Marcia N Gordon; Bryce Chackerian; Jennifer Alamed; Kenneth E Ugen; Dave Morgan
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology     Volume:  5     ISSN:  1557-1904     ISO Abbreviation:  J Neuroimmune Pharmacol     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-02     Completed Date:  2010-05-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101256586     Medline TA:  J Neuroimmune Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  133-42     Citation Subset:  IM    
Affiliation:
Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / drug therapy*,  immunology,  metabolism,  pathology,  prevention & control
Amyloid beta-Protein / chemistry,  immunology,  metabolism
Amyloid beta-Protein Precursor / genetics*
Animals
Brain / immunology,  metabolism,  pathology
Disease Models, Animal
Drug Carriers / chemical synthesis,  therapeutic use
Immunoglobulin G / blood
Immunoglobulin M / blood
Mice
Mice, Transgenic
Vaccination / methods
Vaccines, Subunit / administration & dosage,  chemical synthesis*
Virion / chemistry,  immunology*
Grant Support
ID/Acronym/Agency:
AG15490/AG/NIA NIH HHS; AG18478/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Protein; 0/Amyloid beta-Protein Precursor; 0/Drug Carriers; 0/Immunoglobulin G; 0/Immunoglobulin M; 0/Vaccines, Subunit

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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