Efficient Expression of an Alzheimer's Disease Vaccine Candidate in the Microalga Schizochytrium sp. Using the Algevir System

Mol Biotechnol. 2018 May;60(5):362-368. doi: 10.1007/s12033-018-0077-4.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease, where β-amyloid (Aβ) plays a key role in forming conglomerated senile plaques. The receptor of advanced glycation end products (RAGE) is considered a therapeutic target since it transports Aβ into the central nervous system, favoring the pathology progression. Due to the lack of effective therapies for AD, several therapeutic approaches are under development, being vaccines considered a promising alternative. Herein, the use of the Algevir system was explored to produce in the Schizochytrium sp. microalga the LTB:RAGE vaccine candidate. Algevir relies in an inducible geminiviral vector and led to yields of up to 380 µg LTB:RAGE/g fresh weight biomass at 48-h post-induction. The Schizochytrium-produced LTB:RAGE vaccine retained its antigenic activity and was highly stable up to temperatures of 60 °C. These data demonstrate the potential of Schizochytrium sp. as a platform for high production of thermostable recombinant antigens useful for vaccination against AD.

Keywords: Algae-based vaccine; Alzheimer’s disease; Receptor for advanced glycation end products; Recombinant protein yield.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Alzheimer Vaccines / genetics
  • Alzheimer Vaccines / metabolism*
  • Alzheimer Vaccines / pharmacology
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / genetics*
  • Bacterial Toxins / metabolism
  • Cloning, Molecular
  • Enterotoxins / chemistry
  • Enterotoxins / genetics*
  • Enterotoxins / metabolism
  • Epitopes / genetics
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Humans
  • Microalgae / growth & development*
  • Microalgae / metabolism
  • Protein Engineering
  • Receptor for Advanced Glycation End Products / antagonists & inhibitors
  • Receptor for Advanced Glycation End Products / chemistry*
  • Receptor for Advanced Glycation End Products / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology

Substances

  • Alzheimer Vaccines
  • Bacterial Toxins
  • Enterotoxins
  • Epitopes
  • Escherichia coli Proteins
  • Receptor for Advanced Glycation End Products
  • Recombinant Fusion Proteins
  • heat-labile enterotoxin, E coli