Intradermal active full-length DNA Aβ42 immunization via electroporation leads to high anti-Aβ antibody levels in wild-type mice

J Neuroimmunol. 2018 Sep 15:322:15-25. doi: 10.1016/j.jneuroim.2018.05.017. Epub 2018 Jun 11.

Abstract

Aβ immunotherapies with anti-Aβ antibody responses have high potential as possible prevention treatment for Alzheimer's disease. We have previously shown that active DNA Aβ1-42 immunization via gene gun delivery led to a non-inflammatory immune response resulting in decreased Aβ levels in brains of an immunized AD mouse model. To make DNA vaccination more applicable for clinical use, we used here intradermal electroporation. With fine tuning of the electropulse parameters, high antibody levels and low levels of inflammatory cytokines in the cellular immunoassays were observed. Full-length DNA Aβ1-42 immunization delivered via electroporation has potential to be used in the clinical setting.

Keywords: Alzheimer's disease; DNA Aβ42 immunotherapy; DNA vaccination; Electroporation; IgG isotypes; Immune response; Intradermal immunization; Non-inflammatory; Pulse parameter.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / prevention & control
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / immunology*
  • Animals
  • Antibody Formation
  • Biolistics
  • Dose-Response Relationship, Immunologic
  • Electromagnetic Phenomena
  • Electroporation / methods*
  • Forkhead Transcription Factors / genetics
  • Genes, Reporter
  • Humans
  • Immunization / methods*
  • Immunogenicity, Vaccine
  • Injections, Intradermal
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology*
  • Plaque, Amyloid / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*

Substances

  • Amyloid beta-Peptides
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Peptide Fragments
  • Vaccines, DNA
  • amyloid beta-protein (1-42)