Delivery of a DNA vaccine for Alzheimer's disease by electroporation versus gene gun generates potent and similar immune responses

Neurodegener Dis. 2012;10(1-4):261-4. doi: 10.1159/000333359. Epub 2012 Feb 1.

Abstract

Background: Induction of a humoral response against amyloid-β peptide may be beneficial for Alzheimer's disease (AD) patients and may alleviate the onset and progression of AD. DNA-based vaccination provides a unique alternative method of immunization for treatment and prevention of AD. Currently, the two major delivery methods used for enhancing DNA uptake and immune responses to DNA vaccines in humans are electroporation (EP) and gene gun (GG).

Objective: The goal of this translational study was to evaluate the efficacy of an AD DNA epitope vaccine (DepVac) delivered intramuscularly by EP or intradermally by GG.

Methods: Humoral and cellular immune responses to immunization with DepVac were evaluated by ELISA and ELISPOT, respectively. Functional activity of the antibodies was also assessed.

Results: EP- and GG-mediated immunizations with DepVac induced similar anti-amyloid-β (Aβ) antibody and T cell responses. Anti-Aβ antibodies bound to amyloid plaques in AD brain tissue and to toxic forms of Aβ(42) peptide.

Conclusion: Both delivery methods are effective at promoting potent antibodies specific for Aβ.

Publication types

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

MeSH terms

  • Alzheimer Disease* / blood
  • Alzheimer Disease* / immunology
  • Alzheimer Disease* / therapy
  • Amyloid beta-Peptides / immunology*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Antibodies / blood*
  • Biolistics / methods
  • Disease Models, Animal
  • Electroporation / methods*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Epitopes / immunology
  • Malaria Vaccines / immunology
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Thymidine / metabolism
  • Time Factors
  • Tritium / metabolism
  • Vaccines, DNA / administration & dosage*

Substances

  • Amyloid beta-Peptides
  • Antibodies
  • Epitopes
  • Malaria Vaccines
  • PADRE 45
  • Peptide Fragments
  • Vaccines, DNA
  • amyloid beta-protein (1-42)
  • Tritium
  • Thymidine