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

Abstract

A key molecule in the pathogenesis of Alzheimer's disease (AD) is a 42-amino acid isoform of the amyloid-b peptide (Ab42), 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)-Ab42 fusion protein was successfully expressed in silkworm pupae. We tested the silkworm pupae-derived oral vaccination containing CTB-Ab42 in a transgenic mouse model of AD. Anti-Ab42 antibodies were induced in these mice, leading to a decreased Ab 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-Ab42 silkworm pupae-derived vaccine has potential clinical application in the prevention of AD.