Analysis of three plasmid systems for use in DNA A beta 42 immunization as therapy for Alzheimer's disease.
In an effort to optimize DNA immunization-elicited antibody production responses against A beta 1-42 (A beta 42) as a therapy for Alzheimer's disease (AD), comparisons were made between three distinct plasmid systems using gene gun delivery. Plasmids encoding A beta 42 monomer and a novel A beta 42 trimeric fusion protein were evaluated in conjunction with CMV or Gal4/UAS promoter elements. It was found that vaccination A beta 42 trimer under the Gal4/UAS promoter elicited high levels of anti-A beta 42 antibody production. Serum antibody levels from Gal4/UAS-A beta 42 trimer immunized mice were found to be 16.6+/-5.5 microg/ml compared to 6.5+/-2.5 microg/ml with Gal4/UAS-A beta 42 monomer or even less with CMV-A beta 42 trimer. As compared to monomeric A beta 42 or A beta 42 trimer expressed under the CMV promoter, injection of the Gal4/UAS-A beta 42 trimer induced high levels of A beta 42 antigen expression in tissue suggesting a mechanism for the increase in anti-A beta 42 antibody. Antibodies were found to be primarily IgG1 suggesting a predominant Th2 response (IgG1/IgG2a ratio of 9). Serum from A beta 42 trimer-vaccinated mice was also found to identify amyloid plaques in the brains of APP/PS1 transgenic mice. These results demonstrate the potential therapeutic use of Gal4/UAS DNA A beta 42 trimer immunization in preventing Alzheimer's disease.
Qu
Bao-Xi
BX
Alzheimer's Disease Center, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9036, USA.
Lambracht-Washington
Doris
D
Fu
Min
M
Eagar
Todd N
TN
Stüve
Olaf
O
Rosenberg
Roger N
RN
D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy*; D023582:Alzheimer Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D058225:Plaque, Amyloid / Q000276:immunology; D010957:Plasmids / Q000627:therapeutic use*; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G; D010446:Peptide Fragments; D019444:Vaccines, DNA; C075222:amyloid beta-protein (1-42)