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.