In silico detection of SARS-CoV-2 specific B-cell epitopes and validation in ELISA for serological diagnosis of COVID-19

Phan, I. Q.; Subramanian, S.; Kim, D.; Carter, L.; King, N.; Anishchenko, I.; Barrett, L. K.; Craig, J. K.; Tillery, L.; Shek, R.; Harrington, W. E.; Koelle, D. M.; Wald, A.; Boonyaratanakornkit, J.; Isoherranen, N.; Greninger, A. L.; Jerome, K. R.; Chu, H.; Staker, B.; Myler, P. J.; Van Voorhis, W. C.

doi:10.1101/2020.05.22.111526

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bioRxiv · 10.1101/2020.05.22.111526

In silico detection of SARS-CoV-2 specific B-cell epitopes and validation in ELISA for serological diagnosis of COVID-19

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Abstract

Rapid generation of diagnostics is paramount to understand epidemiology and to control the spread of emerging infectious diseases such as COVID-19. Computational methods to predict serodiagnostic epitopes that are specific for the pathogen could help accelerate the development of new diagnostics. A systematic survey of 27 SARS-CoV-2 proteins was conducted to assess whether existing B-cell epitope prediction methods, combined with comprehensive mining of sequence databases and structural data, could predict whether a particular protein would be suitable for serodiagnosis. Nine of the predictions were validated with recombinant SARS-CoV-2 proteins in the ELISA format using plasma and sera from patients with SARS-CoV-2 infection, and a further 11 predictions were compared to the recent literature. Results appeared to be in agreement with 12 of the predictions, in disagreement with 3, while a further 5 were deemed inconclusive. We showed that two of our top five candidates, the N-terminal fragment of the nucleoprotein and the receptor-binding domain of the spike protein, have the highest sensitivity and specificity and signal-to-noise ratio for detecting COVID-19 sera/plasma by ELISA. Mixing the two antigens together for coating ELISA plates led to a sensitivity of 94% (N=80 samples from persons with RT-PCR confirmed SARS-CoV2 infection), and a specificity of 97.2% (N=106 control samples).

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Phan, I. Q., Subramanian, S., Kim, D., Carter, L., King, N., Anishchenko, I., Barrett, L. K., Craig, J. K., Tillery, L., Shek, R., Harrington, W. E., Koelle, D. M., Wald, A., Boonyaratanakornkit, J., Isoherranen, N., Greninger, A. L., Jerome, K. R., Chu, H., Staker, B., Myler, P. J., Van Voorhis, W. C.. 2020-05-23. In silico detection of SARS-CoV-2 specific B-cell epitopes and validation in ELISA for serological diagnosis of COVID-19. https://doi.org/10.1101/2020.05.22.111526

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