Induction of a Th2 immune response by co-administration of recombinant adenovirus vectors encoding amyloid β-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 β-protein (Aβ) is effective in prevention and clearance of deposits of Aβ aggregates in the brain of the mice. We have tested a non-injection modality whereby replication-defective adenovirus vectors encoding Aβ or the 99-amino acid carboxyl terminal fragment of Aβ precursor were intranasally administered to mice to elicit immune responses against Aβ. When mice were immunized only with the adenovirus vectors, immune responses against Aβ were negligible. By co-immunization with an adenovirus vector encoding granulocyte-macrophage colony stimulating factor (GM-CSF), the adenovirus vector encoding Aβ effectively elicited an immune response against Aβ. 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 Aβ by adenovirus-mediated nasal vaccination.