Induction of anti-inflammatory immune response by an adenovirus vector encoding 11 tandem repeats of Abeta1-6: toward safer and effective vaccines against Alzheimer's disease |
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Authors: | Kim Hong-Duck Maxwell J Adam Kong Fan-Kun Tang De-chu C Fukuchi Ken-ichiro |
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Institution: | Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, P.O. Box 1649, Peoria, IL 61656, USA. |
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Abstract: | Induction of an immune response to amyloid beta-protein (Abeta) is effective in treating animal models of Alzheimer's disease. Human clinical trials of vaccination with synthetic Abeta (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 Abeta1-6 can induce an immune response against amyloid beta-protein. Much higher titers against amyloid beta-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 Abeta1-6 may be a safer alterative to peptide-based vaccines. |
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Keywords: | Alzheimer’s disease Vaccine Adenovirus Amyloid Transgenic mice Immunization ELISA Antibody GM-CSF Self protein |
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