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; Zhen Wei; Jian Chen; Yanhong Chen; Zhengbing Lv; Wei Yu; Qiaohong Meng; Yongfeng Jin

doi:10.1371/journal.pone.0113585

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

PLoS One. 2014 Dec 3;9(12):e113585. doi: 10.1371/journal.pone.0113585. eCollection 2014.

Authors

Si Li¹, Zhen Wei², Jian Chen³, Yanhong Chen², Zhengbing Lv³, Wei Yu³, Qiaohong Meng⁴, Yongfeng Jin⁵

Affiliations

¹ Institute of Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou, China; Institute of Biochemistry, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
² Laboratory Animal Center of Zhejiang University, Zhejiang University, Hangzhou, China.
³ Institute of Biochemistry, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
⁴ Institute of Aging Research, School of Medicine, Hangzhou Normal University, Hangzhou, China.
⁵ Institute of Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Alzheimer Disease / physiopathology
Alzheimer Disease / therapy*
Alzheimer Vaccines / administration & dosage*
Alzheimer Vaccines / genetics
Amyloid beta-Peptides / genetics
Amyloid beta-Peptides / metabolism*
Animals
Animals, Genetically Modified
Bombyx / growth & development*
Bombyx / metabolism
Cells, Cultured
Cholera Toxin / genetics*
Cholera Toxin / metabolism
Disease Models, Animal
Male
Maze Learning
Mice
Peptide Fragments / genetics
Peptide Fragments / metabolism*
Protein Isoforms / genetics
Protein Isoforms / metabolism
Pupa / metabolism
Recombinant Fusion Proteins / administration & dosage
Recombinant Fusion Proteins / genetics

Substances

Alzheimer Vaccines
Amyloid beta-Peptides
Peptide Fragments
Protein Isoforms
Recombinant Fusion Proteins
amyloid beta-protein (1-42)
Cholera Toxin

Grants and funding

This work was financially supported by research grants from the Natural Science Foundation of Zhejiang Province (Y3110354), National High Technology Research and Development Programs of China (2012ZX09102301-009, 2011AA100603), the Open Fund of Zhejiang Provincial Top Key Discipline of Biology, and the Project of Education Department of Zhejiang Province (Z201018783, Y200909617). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.