Oral administration of a fusion protein between the cholera toxin B subunit and the 42-amino acid isoform of amyloid-β peptide produced in silkworm pupae protects against Alzheimer's disease in mice.

Si Li,Jian Chen,Zhengbing Lv,Wei Yu,Zhen Wei,Yongfeng Jin,Qiaohong Meng,Yanhong Chen,Jie Zheng

doi:10.1371/journal.pone.0113585

Si Li, Jian Chen + Show 7 more

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https://doi.org/10.1371/journal.pone.0113585

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Abstract

A key molecule in the pathogenesis of Alzheimer's disease (AD) is a 42-amino acid isoform of the amyloid-β peptide (Aβ42), which is the most toxic element of senile plaques. In this study, to develop an edible, safe, low-cost vaccine for AD, a cholera toxin B subunit (CTB)-Aβ42 fusion protein was successfully expressed in silkworm pupae. We tested the silkworm pupae-derived oral vaccination containing CTB-Aβ42 in a transgenic mouse model of AD. Anti-Aβ42 antibodies were induced in these mice, leading to a decreased Aβ deposition in the brain. We also found that the oral administration of the silk worm pupae vaccine improved the memory and cognition of mice, as assessed using a water maze test. These results suggest that the new edible CTB-Aβ42 silkworm pupae-derived vaccine has potential clinical application in the prevention of AD.

Highlights

The main neuropathological feature of Alzheimer’s disease (AD) is excessive extracellular b-amyloid protein (Ab) deposition that forms senile plaques
A vaccine producing a mild antigen-antibody reaction and/or an appropriate immunological adjuvant resulting in a decreased TH1 immune response and an increased TH2 immune response is needed for the prevention and treatment of AD
The recombinant plasmid pBacPAK8-cholera toxin B subunit (CTB)-Ab42 and linearized BmNPV DNA digested with Bsu36I were co-transfected in BmN cells

Summary

Introduction

The main neuropathological feature of Alzheimer’s disease (AD) is excessive extracellular b-amyloid protein (Ab) deposition that forms senile plaques. The Ab vaccine has been shown to decrease and eliminate Ab deposition in the brains of AD transgenic mice and to impair behavioral and cognitive disorders in experimental mice [3,4]. A phase II clinical trial on the Ab injection vaccine AN1792, produced by the ELAN corporation, was initiated, but the trial was stopped prematurely because aseptic meningitis occurred in 6% of trial subjects [5,6]. This reaction is related to the induction of TH1-type responses. A vaccine producing a mild antigen-antibody reaction and/or an appropriate immunological adjuvant resulting in a decreased TH1 immune response and an increased TH2 immune response is needed for the prevention and treatment of AD

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