DNA epitope vaccine containing complement component C3d enhances anti-amyloid-beta antibody production and polarizes the immune response towards a Th2 phenotype

J Neuroimmunol. 2008 Dec 15;205(1-2):57-63. doi: 10.1016/j.jneuroim.2008.08.016. Epub 2008 Oct 5.

Abstract

We have engineered a DNA epitope vaccine that expresses 3 self-B cell epitopes of Abeta(42) (3Abeta(1-11)), a non-self T helper (Th) cell epitope (PADRE), and 3 copies of C3d (3C3d), a component of complement as a molecular adjuvant, designed to safely reduce CNS Abeta. Immunization of mice with 3Abeta(1-11)-PADRE epitope vaccine alone generated only moderate levels of anti-Abeta antibodies and a pro-inflammatory T helper (Th1 phenotype) cellular immune response. However, the addition of 3C3d to the vaccine construct significantly augmented the anti-Abeta humoral immune response and, importantly, shifted the cellular immune response towards the potentially safer anti-inflammatory Th2 phenotype.

Publication types

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

MeSH terms

  • Amyloid beta-Peptides / immunology*
  • Analysis of Variance
  • Animals
  • CHO Cells
  • Complement C3d / genetics
  • Complement C3d / immunology*
  • Cricetinae
  • Cricetulus
  • Cytokines / metabolism
  • Dose-Response Relationship, Immunologic
  • Enzyme-Linked Immunosorbent Assay / methods
  • Epitopes / genetics
  • Epitopes / immunology*
  • Female
  • Immunoglobulin G / classification
  • Immunoglobulin G / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transfection
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*

Substances

  • Amyloid beta-Peptides
  • Cytokines
  • Epitopes
  • Immunoglobulin G
  • Peptide Fragments
  • Vaccines, DNA
  • amyloid beta-protein (1-11)
  • Complement C3d