Intradermal active full-length DNA Aβ42 immunization via electroporation leads to high anti-Aβ antibody levels in wild-type mice with variability in T cell responses depending on pulse parameters applied

Abstract

Abstract Aβ immunotherapy has high potential as possible prevention treatment for Alzheimer’s disease, and anti-Aβ antibodies will help in the removal of excess amyloid from brain. We have previously shown that active DNA Aβ1-42 immunization via gene gun delivery led to a non-inflammatory immune response with efficient antibody levels which resulted in decreased Aβ levels in brains of the immunized AD mouse model mice. To optimize the DNA delivery and make DNA vaccination more applicable for clinical use, we have investigated here the use of intradermal electroporation using a variety of different voltages and electropulse parameters in wild-type mice. In the direct comparison to DNA delivery via gene gun, higher levels of anti-Aβ42 antibodies were detected already after three DNA immunizations. The antibody isotype profile following DNA electroporation was mixed with IgG1 and IgG2a antibodies. With a fine tuning of the electropulse protocol the T cell responses could be adjusted to similar findings we published earlier for DNA Aβ1-42 immunization via gene gun delivery with low levels of inflammatory cytokines (IFNγ, IL-17) in the in-vitro Aβ42 peptide re-stimulation assays. We found that short pulse durations (5 ms) were better than long pulse durations (10 ms) in regard to obtaining a Th2 type of immune response, and that a higher rate of pulses (16–20 pulses) increased the antibody response in our sets of experiments. Full-length DNA Aβ1-42 immunization delivered via electroporation with a fine tuning of the electropulse conditions has potential to be used in the clinical setting.