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

Abstract

We have engineered a DNA epitope vaccine that expresses 3 self-B cell epitopes of Aβ 42 (3Aβ 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 Aβ. Immunization of mice with 3Aβ 1–11-PADRE epitope vaccine alone generated only moderate levels of anti-Aβ 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-Aβ humoral immune response and, importantly, shifted the cellular immune response towards the potentially safer anti-inflammatory Th2 phenotype.