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

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.