Induction of anti-inflammatory immune response by an adenovirus vector encoding 11 tandem repeats of Aβ1-6: Toward safer and effective vaccines against Alzheimer's disease

Induction of an immune response to amyloid β-protein (Aβ) is effective in treating animal models of Alzheimer's disease. Human clinical trials of vaccination with synthetic Aβ (AN1792), however, were halted due to brain inflammation, presumably induced by T cell-mediated immune responses. We have developed an adenovirus vector as a “possibly safer” vaccine. Here, we show that an adenovirus vector encoding 11 tandem repeats of Aβ1-6 can induce an immune response against amyloid β-protein. Much higher titers against amyloid β-protein were observed when an adenovirus vector encoding GM-CSF was co-administered. Immunoglobulin isotyping revealed a predominant IgG1 response, indicating anti-inflammatory Th2 type. Immunohistochemical analysis revealed no inflammation-related pathology in the brain of mice immunized with the adenovirus vector. Induced antibodies strongly reacted with amyloid plaques in the brain, demonstrating functional activity of the antibodies. Thus, the adenovirus vector encoding 11 tandem repeats of Aβ1-6 may be a safer alterative to peptide-based vaccines.