Recombinant SARS-CoV-2 spike S1-Fc fusion protein induced high levels of neutralizing responses in nonhuman primates

Ren, W.; Sun, H.; Gao, G. F.; Chen, J.; Sun, S.; Zhao, R.; Gao, G.; Hu, Y.; Zhao, G.; Chen, Y.; Jin, X.; Fang, F.; Wang, Q.; Gong, S.; Gao, W.; Sun, Y.; Su, J.; He, A.; Cheng, X.; Li, M.; Xia, C.; Sun, L.

doi:10.1101/2020.04.21.052209

bioRxiv · 10.1101/2020.04.21.052209

Recombinant SARS-CoV-2 spike S1-Fc fusion protein induced high levels of neutralizing responses in nonhuman primates

Ren, W.·Sun, H.·Gao, G. F.·Chen, J.·Sun, S.·Zhao, R.·Gao, G.·Hu, Y.·Zhao, G.·Chen, Y.·Jin, X.·Fang, F.·Wang, Q.·Gong, S.·Gao, W.·Sun, Y.·Su, J.·He, A.·Cheng, X.·Li, M.·Xia, C.·Sun, L.

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Abstract

The COVID-19 outbreak has become a global pandemic responsible for over 2,000,000 confirmed cases and over 126,000 deaths worldwide. In this study, we examined the immunogenicity of CHO-expressed recombinant SARS-CoV-2 S1-Fc fusion protein in mice, rabbits, and monkeys as a potential candidate for a COVID-19 vaccine. We demonstrate that the S1-Fc fusion protein is extremely immunogenic, as evidenced by strong antibody titers observed by day 7. Strong virus neutralizing activity was observed on day 14 in rabbits immunized with the S1-Fc fusion protein using a pseudovirus neutralization assay. Most importantly, in less than 20 days and three injections of the S1-Fc fusion protein, two monkeys developed higher virus neutralizing titers than a recovered COVID-19 patient in a live SARS-CoV-2 infection assay. Our data strongly suggests that the CHO-expressed SARS-CoV-2 S1-Fc recombinant protein could be a strong candidate for vaccine development against COVID-19. HighlightsO_LICHO-expressed S1-Fc protein is very immunogenic in various animals and can rapidly induce strong antibody production C_LIO_LIS1-Fc protein solicits strong neutralizing activities against live virus C_LIO_LIStable CHO cell line expressing 50 mg/L of S1-Fc and a 3,000 L Bioreactor can produce 3 million doses of human COVID-19 vaccine every 10 days, making it an accessible and affordable option for worldwide vaccination C_LI

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Ren, W., Sun, H., Gao, G. F., Chen, J., Sun, S., Zhao, R., Gao, G., Hu, Y., Zhao, G., Chen, Y., Jin, X., Fang, F., Wang, Q., Gong, S., Gao, W., Sun, Y., Su, J., He, A., Cheng, X., Li, M., Xia, C., Sun, L.. 2020-04-23. Recombinant SARS-CoV-2 spike S1-Fc fusion protein induced high levels of neutralizing responses in nonhuman primates. https://doi.org/10.1101/2020.04.21.052209

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