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.
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.
Kim
Hong-Duck
HD
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, P.O. Box 1649, Peoria, IL 61656, USA.
Maxwell
J Adam
JA
Kong
Fan-Kun
FK
Tang
De-chu C
DC
Fukuchi
Ken-ichiro
K
D000256:Adenoviridae / Q000235:genetics*; D000544:Alzheimer Disease / Q000276:immunology / Q000517:prevention & control*; D023582:Alzheimer Vaccines / Q000235:genetics* / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000276:immunology; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary; D004591:Electrophoresis, Polyacrylamide Gel; D005822:Genetic Vectors; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D020080:Tandem Repeat Sequences
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D018076:DNA, Complementary; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C505239:amyloid beta-protein (1-6)