Immunization of Alzheimer model mice with adenovirus vectors encoding amyloid beta-protein and GM-CSF reduces amyloid...

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.