Immunization of Alzheimer model mice with adenovirus vectors encoding amyloid beta-protein and GM-CSF reduces amyloid load in the brain.
Induction of anti-amyloid beta-protein (Abeta) antibodies in transgenic mouse models of Alzheimer disease (AD) by repeated injection of synthetic Abeta was shown to be effective in preventing and removing deposition of Abeta aggregates in the brain. Here, we have tested a non-invasive modality whereby a replication-defective adenovirus vector encoding Abeta was intranasally administered to mice to elicit immune responses against Abeta. Intranasal immunization only with the adenovirus vector failed to induce significant immune responses. When an adenovirus vector encoding granulocyte/macrophage-colony stimulating factor (GM-CSF) was used as an adjuvant in conjunction with the adenovirus encoding Abeta, a marked immune response was elicited against Abeta. Immunoglobulin isotyping revealed that the induced anti-Abeta antibodies are predominantly of the IgG2b and IgG1 isotypes, suggesting a Th-2 anti-inflammatory type. Furthermore, amyloid load in the brain of AD model mice (Tg2576) vaccinated with adenovirus vectors encoding Abeta and GM-CSF was much smaller than that in control Tg2576 mice. Thus, intranasal administration of adenovirus vectors encoding Abeta and GM-CSF may be effective in prevention and treatment of AD.
Department of Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, KHGB 640B, 720 20th Street South, Birmingham, AL 35294-0024, USA.
Hong-Duck
HD
Kim
Fan-Kun
FK
Kong
Yunpeng
Y
Cao
Terry L
TL
Lewis
Helen
H
Kim
De-chu C
DC
Tang
Ken-ichiro
K
Fukuchi
D000256:Adenoviridae / Q000235:genetics; D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002460:Cell Line; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015316:Genetic Therapy; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007136:Immunoglobulins / Q000145:classification / Q000627:therapeutic use; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics
D000682:Amyloid; D016229:Amyloid beta-Peptides; D007136:Immunoglobulins; D010446:Peptide Fragments; D025521:Tumor Suppressor Proteins; C075222:amyloid beta-protein (1-42); D016178:Granulocyte-Macrophage Colony-Stimulating Factor