From a recombinant key antigen to an accurate, affordable serological test: Lessons learnt from COVID-19 for future pandemics

Serological tests detect antibodies generated by infection or vaccination, and are indispensable tools along different phases of a pandemic, from early monitoring of pathogen spread up to seroepidemiological studies supporting immunization policies. This work discusses the development of an accurate and affordable COVID-19 antibody test, from production of a recombinant protein antigen up to test validation and economic analysis. We first developed a cost-effective, scalable technology to produce SARS-COV-2 spike protein and then used this antigen to develop an enzyme-linked immunosorbent assay (ELISA). A receiver operator characteristic (ROC) analysis allowed optimizing the cut-off and confirmed the high accuracy of the test: 98.6% specificity and 95% sensitivity for 11+ days after symptoms onset. We further showed that dried blood spots collected by finger pricking on simple test strips could replace conventional plasma/serum samples. A cost estimate was performed and revealed a final retail price in the range of one US dollar, reflecting the low cost of the ELISA test platform and the elimination of the need for venous blood sampling and refrigerated sample handling in clinical laboratories. The presented workflow can be completed in 4 months from first antigen expression to final test validation. It can be applied to other pathogens and in future pandemics, facilitating reliable and affordable seroepidemiological surveillance also in remote areas and in low-income countries.

Automated summary

This study discusses the development of an accurate and affordable COVID-19 antibody test, including the production of a recombinant protein antigen and the validation of an enzyme-linked immunosorbent assay (ELISA). The test showed high accuracy with 98.6% specificity and 95% sensitivity, and dried blood spots collected on test strips could replace conventional plasma/serum samples. The estimated cost was low, and the entire process could be completed in four months. This research is important for reliable and affordable seroepidemiological surveillance during pandemics.