Plasmablast-derived antibody response to acute SARS-CoV-2 infection in humans

Huang, K.-Y. A.; Tan, T.; Chen, T.-H.; Huang, C.-G.; Harvey, R.; Hussain, S.; Chen, C.-P.; Harding, A.; Gilbert-Jaramillo, J.; Liu, X.; Knight, M.; Schimanski, L.; Shih, S.-R.; Lin, Y.-C.; Cheng, C.-Y.; Cheng, S.-H.; Huang, Y.-C.; Lin, T.-Y.; Rahikainen, R.; Howarth, M.; Jan, J.-T.; Ma, C.; James, W. S.; Daniels, R.; McCauley, J.; Rijal, P.; Townsend, A.

doi:10.1101/2020.08.28.267526

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bioRxiv · 10.1101/2020.08.28.267526

Plasmablast-derived antibody response to acute SARS-CoV-2 infection in humans

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Abstract

Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 13.0% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) and over half of anti-nucleocapsid (19 of 35) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-RBD, three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. At last, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.

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Huang, K.-Y. A., Tan, T., Chen, T.-H., Huang, C.-G., Harvey, R., Hussain, S., Chen, C.-P., Harding, A., Gilbert-Jaramillo, J., Liu, X., Knight, M., Schimanski, L., Shih, S.-R., Lin, Y.-C., Cheng, C.-Y., Cheng, S.-H., Huang, Y.-C., Lin, T.-Y., Rahikainen, R., Howarth, M., Jan, J.-T., Ma, C., James, W. S., Daniels, R., McCauley, J., Rijal, P., Townsend, A.. 2020-08-28. Plasmablast-derived antibody response to acute SARS-CoV-2 infection in humans. https://doi.org/10.1101/2020.08.28.267526

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