title: A coimmunization vaccine of Aβ42 ameliorates cognitive deficits without brain inflammation in an Alzheimer's disease model.
abstract: BACKGROUND
  Vaccination against amyloid-β protein (Aβ42) 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 Aβ42 vaccine induces CD4(+) T cell infiltrations into the central nervous system. To reduce T-cell activation while concomitantly maintaining high anti-Aβ42 titers is a great challenge in immunology.
  
  
  METHODS
  We aimed to demonstrate that coimmunization with Aβ42 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 Aβ42 deposition. Furthermore, to determine the safety of the coimmunization vaccine, we used an induced Aβ42-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.
  
  
  RESULTS
  The coimmunization vaccination reduced Aβ 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.
  
  
  CONCLUSIONS
  A coimmunization strategy leading to the development of a safe immunotherapeutic/preventive protocol against AD in humans is warranted.
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, 131 Dong An Road, Shanghai 200032, China ; State Key Laboratory for Agro-Biotechnology and College of Biologic Sciences, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Agro-Biotechnology and College of Biologic Sciences, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China ; Present address: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, 131 Dong An Road, Shanghai 200032, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Geng
authors.affiliation: Chinese Academy of Medical Sciences & Comparative Medical Center, 5 South Panjiayuan, Beijing 100021, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Chinese Academy of Medical Sciences & Comparative Medical Center, 5 South Panjiayuan, Beijing 100021, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Agro-Biotechnology and College of Biologic Sciences, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xie
authors.affiliation: State Key Laboratory for Agro-Biotechnology and College of Biologic Sciences, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, 131 Dong An Road, Shanghai 200032, China.
authors.forename: Chaofan
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory for Agro-Biotechnology and College of Biologic Sciences, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Hanqian
authors.initials: H
authors.lastname: Xu
authors.affiliation: Institute for Age Research, Fritz Lipmann Institute, Beutenbergstraße 11, Jena D-07745, Germany.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Chinese Academy of Medical Sciences & Comparative Medical Center, 5 South Panjiayuan, Beijing 100021, China.
authors.forename: Lianfeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute for Age Research, Fritz Lipmann Institute, Beutenbergstraße 11, Jena D-07745, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaether
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, 131 Dong An Road, Shanghai 200032, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang