A coimmunization vaccine of A beta 42 ameliorates cognitive deficits without brain inflammation in an Alzheimer's disease model

• Published in: Alzheimer's research & therapy Vol. 6; no. 3; p. 26
• Main Authors: Wang, Shuang, Yu, Yang, Geng, Shuang, Wang, Dongmei, Zhang, Li, Xie, Xiaoping, Wu, Bing, Li, Chaofan, Xu, Hanqian, Li, Xiaolin, Hu, Yanxin, Zhang, Lianfeng, Kaether, Christoph, Wang, Bin
• Format: Journal Article
• Language: English
• Published: 12-05-2014
• ISSN: 1758-9193
• DOI: 10.1186/alzrt256

Vaccination against amyloid- beta protein (A beta 42) induces high levels of antibody, making it a promising strategy for treating Alzheimer's disease (AD). One drawback in the past was that clinical trial approval was withheld because of speculation that the A beta 42 vaccine induces CD4+ T cell infiltrations into the central nervous system. To reduce T-cell activation while concomitantly maintaining high anti-A beta 42 titers is a great challenge in immunology. We aimed to demonstrate that coimmunization with A beta 42 protein and expression plasmid can be beneficial in a mouse AD model and can prevent inflammation. We immunized the AD mice with the coimmunization vaccine and assessed behavior change and A beta 42 deposition. Furthermore, to determine the safety of the coimmunization vaccine, we used an induced A beta 42-EAE model to mimic the meningoencephalitis that happened in the AN-1792 vaccine clinical phase II trial and tested whether the coimmunization vaccine could ameliorate T-cell-mediated brain inflammation. The coimmunization vaccination reduced A beta plaques and significantly ameliorated cognitive deficit while inhibiting T-cell-mediated brain inflammation and infiltration. These studies demonstrate that the coimmunization strategy that we describe in this article can ameliorate AD pathology without notable adverse effects in mice. A coimmunization strategy leading to the development of a safe immunotherapeutic/preventive protocol against AD in humans is warranted.