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


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9108, USA.
Doris
D
Lambracht-Washington
Bao-Xi
BX
Qu
Min
M
Fu
Todd N
TN
Eagar
Olaf
O
Stüve
Roger N
RN
Rosenberg
D000276:Adjuvants, Immunologic; D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D016233:Immunotherapy, Active; D051379:Mice; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D016229:Amyloid beta-Peptides; D016207:Cytokines; D007074:Immunoglobulin G; D010446:Peptide Fragments; D019444:Vaccines, DNA; C075222:amyloid beta-protein (1-42)