Rapid and cost-effective process based on insect larvae for scale-up production of SARS-COV-2 spike protein for serological COVID-19 testing

Biotechnol Bioeng. 2021 Oct;118(10):4129-4137. doi: 10.1002/bit.27889. Epub 2021 Jul 23.

Abstract

Serology testing for COVID-19 is important in evaluating active immune response against SARS-CoV-2, studying the antibody kinetics, and monitoring reinfections with genetic variants and new virus strains, in particular, the duration of antibodies in virus-exposed individuals and vaccine-mediated immunity. In this study, recombinant S protein of SARS-CoV-2 was expressed in Rachiplusia nu, an important agronomic plague. One gram of insect larvae produces an amount of S protein sufficient for 150 determinations in the ELISA method herein developed. We established a rapid production process for SARS-CoV-2 S protein that showed immunoreactivity for anti-SARS-CoV-2 antibodies and was used as a single antigen for developing the ELISA method with high sensitivity (96.2%) and specificity (98.8%). Our findings provide an efficient and cost-effective platform for large-scale S protein production, and the scale-up is linear, thus avoiding the use of complex equipment like bioreactors.

Keywords: ELISA; SARS-CoV-2 coronavirus; antibodies; insect larvae; trimeric spike.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COVID-19 / diagnosis*
  • COVID-19 Serological Testing*
  • Larva / metabolism
  • Larva / virology
  • Nucleopolyhedroviruses
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / metabolism
  • Sf9 Cells
  • Spike Glycoprotein, Coronavirus / biosynthesis*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics
  • Spodoptera

Substances

  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • Autographa californica multiple nuclear polyhedrosis virus