Epitope-based DNA vaccine for Alzheimer's disease: translational study in macaques

Alzheimers Dement. 2014 May;10(3):284-95. doi: 10.1016/j.jalz.2013.04.505. Epub 2013 Jul 31.

Abstract

Background: Clinical trials with passive and active Alzheimer's disease (AD) vaccines suggest that early interventions are needed for improvement of cognitive and/or functional performance in patients, providing impetus for the development of safe and immunologically potent active vaccines targeting amyloid β (Aβ). The AN-1792 trial has indicated that Aβ-specific T cells may be unsafe for humans; therefore, other vaccines based on small Aβ epitopes are undergoing preclinical and clinical testing.

Methods: Humoral and cellular immune responses elicited in response to a novel DNA epitope-based vaccine (AV-1955) delivered to rhesus macaques using the TriGrid electroporation device were evaluated. Functional activities of anti-Aβ antibodies generated in response to vaccination were assessed in vitro.

Results: AV-1955 generates long-term, potent anti-Aβ antibodies and cellular immune responses specific to foreign T-helper epitopes but not to self-Aβ.

Conclusions: This translational study demonstrates that a DNA-based epitope vaccine for AD could be appropriate for human clinical testing.

Keywords: Alzheimer's disease; Amyloid beta; Antibody response; Cellular immune response; DNA vaccine; Electroporation; Epitope vaccine; Rhesus macaques; Translational.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / immunology*
  • Alzheimer Disease / therapy*
  • Alzheimer Vaccines / therapeutic use*
  • Amyloid beta-Peptides / immunology
  • Animals
  • Antibodies / blood
  • Antibodies / immunology
  • Cell Line, Tumor
  • Dose-Response Relationship, Immunologic
  • Epitopes, T-Lymphocyte
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Longitudinal Studies
  • Lymphocyte Activation*
  • Macaca mulatta
  • Male
  • Plaque, Amyloid / immunology
  • Random Allocation
  • T-Lymphocytes, Helper-Inducer / physiology*
  • Time Factors
  • Translational Research, Biomedical
  • Vaccines, DNA / immunology
  • Vaccines, DNA / therapeutic use

Substances

  • Alzheimer Vaccines
  • Amyloid beta-Peptides
  • Antibodies
  • Epitopes, T-Lymphocyte
  • Immunoglobulin G
  • Vaccines, DNA