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

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. A rapid and cost‐effective process for scale‐up the production of SARS‐CoV‐2 Spike protein was developed in this study. The authors obtained high‐quality protein (trimeric and glycosylated state) after one step of purification from Rachiplusia nu larvae. Our results demonstrate that the Spike protein produced in insect larvae is immunoreactive against the sera from COVID‐19 patients and can be used as a single antigen in immunoassays for the detection of anti‐SARS‐Cov‐2 antibodies