DNA immunization with HBsAg-based particles expressing a B cell epitope of amyloid beta-peptide attenuates disease progression and prolongs survival in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is an incurable and progressive neurodegenerative senile disorder associated with the brain accumulation of A beta plaques. Although vaccines that reduce A beta plaques can control AD, the rationale for their use at the onset of the disease remains debatable. Old humans and mice usually respond poorly to vaccines due to presumably age-related immunological impairments. Here, we report that by modifying vaccines, the poor responsiveness of old mice can be reversed. Unlike the A beta peptide vaccine, DNA immunizations with the amino-terminal A beta(1-11) fragment exposed on the surface of HBsAg particles elicit high levels of anti-A beta antibody both in young and old mice. Importantly, in AD model 3xTgAD mice, the vaccine reduced A beta plaques, ameliorated cognitive impairments and, surprisingly, significantly increased life span. Hence, we propose that vaccines targeting A beta(1-11) can efficiently combat AD-induced pathological alterations and provide survival benefit in patients with AD. (C) 2012 Elsevier Ltd. All rights reserved.

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