Epitopes described in "DNA beta-amyloid(1-42) trimer immunization for Alzheimer disease in a wild-type mouse model."

Article Authors:Doris Lambracht-Washington; Bao-Xi Qu; Min Fu; Todd N Eagar; Olaf Stüve; Roger N Rosenberg
Article Title:DNA beta-amyloid(1-42) trimer immunization for Alzheimer disease in a wild-type mouse model.
Reference Detail
Reference ID:1017635
Abstract:CONTEXT: DNA beta-amyloid(1-42) (Abeta42) trimer immunization was developed to produce specific T helper 2 cell (T(H)2)-type antibodies to provide an effective and safe therapy for Alzheimer disease (AD) by reducing elevated levels of Abeta42 peptide that occur in the brain of patients with AD. OBJECTIVE: To compare the immune response in wild-type mice after immunization with DNA Abeta42 trimer and Abeta42 peptide. DESIGN AND INTERVENTION: Wild-type mice received either 4 microg of DNA Abeta42 trimer immunization administered with gene gun (n = 8) or intraperitoneal injection of 100 microg of human Abeta42 peptide with the adjuvant Quil A (n = 8). Titers, epitope mapping, and isotypes of the Abeta42-specific antibodies were analyzed. MAIN OUTCOME MEASURES: Antibody titers, mapping of binding sites (epitopes), isotype profiles of the Abeta42-specific antibodies, and T-cell activation. RESULTS: DNA Abeta42 trimer immunization resulted in antibody titers with a mean of 15 microg per milliliter of plasma. The isotype profile of the antibodies differed markedly. A predominant IgG1 antibody response was found in the DNA-immunized mice, indicating a T(H)2 type of immune response (IgG1/IgG2a ratio of 10). The peptide-immunized mice showed a mixed T(H)1/T(H)2 immune response (IgG1/IgG2a ratio of 1) (P < .001). No increased T-cell proliferation was observed in the DNA-immunized mice (P = .03). CONCLUSION: In this preliminary study in a wild-type mouse model, DNA Abeta42 trimer immunization protocol produced a T(H)2 immune response and appeared to have low potential to cause an inflammatory T-cell response.
Affiliations:Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9108, USA.
Reference Type:Literature
PubMed ID:19861672
Journal Volume:302
Article Pages:1796-802
Journal ISSN:1538-3598
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@11da36dc;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@d47aeac;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5d1ca503;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@39597b7;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@521b7137;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@7a5fbfe;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@2242e49e
Article MeSH List:Adjuvants, Immunologic; Alzheimer Disease(immunology; therapy); Amyloid beta-Peptides(genetics; immunology); Animals; Antibody Formation; Cytokines(biosynthesis); Disease Models, Animal; Epitope Mapping; Female; Humans; Immunoglobulin G(immunology); Immunotherapy, Active; Mice; Peptide Fragments(genetics; immunology); Th1 Cells(immunology); Th2 Cells(immunology); Vaccines, DNA(administration & dosage; immunology; therapeutic use)
Curation Last Updated:2015-01-27 21:18:49