Induction of a Th2 immune response by co-administration of recombinant adenovirus vectors encoding amyloid beta-protein and GM-CSF.
Lines of experimental evidence indicate that induction of humoral immune responses in transgenic mouse models of Alzheimer disease (AD) by repeated injection of synthetic amyloid beta-protein (Abeta) is effective in prevention and clearance of deposits of Abeta aggregates in the brain of the mice. We have tested a non-injection modality whereby replication-defective adenovirus vectors encoding Abeta or the 99-amino acid carboxyl terminal fragment of Abeta precursor were intranasally administered to mice to elicit immune responses against Abeta. When mice were immunized only with the adenovirus vectors, immune responses against Abeta were negligible. By co-immunization with an adenovirus vector encoding granulocyte-macrophage colony stimulating factor (GM-CSF), the adenovirus vector encoding Abeta effectively elicited an immune response against Abeta. Immunoglobulin isotyping demonstrated a predominant IgG1 and IgG2b response, suggesting a Th2 anti-inflammatory type. Thus, adjuvantation is essential for induction of an immune response against Abeta by adenovirus-mediated nasal vaccination.
Kim
Hong-Duck
HD
Department of Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, KHGB 640B, 720 20th Street South, Birmingham, AL 35294-0024, USA.
Cao
Yunpeng
Y
Kong
Fan-Kun
FK
Van Kampen
Kent R
KR
Lewis
Terry L
TL
Ma
Zhendong
Z
Tang
De-chu C
DC
Fukuchi
Ken-Ichiro
K
D000256:Adenoviridae / Q000235:genetics*; D000281:Administration, Intranasal; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology*; D000818:Animals; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018418:Th2 Cells / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor