Developing Novel Immunogens for an Effective, Safe Alzheimer’s Disease Vaccine

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Abstract
Active amyloid β (Aβ) vaccination has been shown to be effective in clearing cerebral Aβ and improving cognitive function in mouse models of Alzheimer’s disease. However, an Aβ vaccine clinical trial was suspended after meningoencephalitis was detected in a subset of subjects. Passive immunization has been suggested to be a safer alternative to active Aβ immunization but there are reports of increased risk of microhemorrhages associated with its administration in aged β-amyloid precursor protein transgenic mice bearing abundant vascular amyloid deposition. In addition, the cost may be prohibitive for large-scale clinical use. Therefore, we are designing novel Aβ immunogens that encompass the B cell epitope of Aβ but lack the T cell-reactive sites. These immunogens induced the production of Aβ-specific antibodies in the absence of an Aβ-specific cellular immune response in wild-type mice and are being tested in β-amyloid precursor protein transgenic mice. These data together with published reports from several other groups suggest that a safe, active Aβ vaccine is a tenable goal.