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

Plasmablast responses and derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients. An average of 13.7% and 13.0% of plasmablast-derived IgG MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. Of thirty-two antibodies specific for the spike glycoprotein, ten recognised the receptor-binding domain (RBD), thirteen were specific for non-RBD epitopes on the S1 subunit, and nine recognised the S2 subunit. A subset of anti-spike antibodies (10 of 32) cross-reacted with other betacoronaviruses tested, five targeted the non-RBD S1, and five targeted the S2 subunit. Of the plasmablast-derived MAbs reacting with nucleocapsid, over half of them (19 of 35) cross-reacted with other betacoronaviruses tested. The cross-reactive plasmablast-derived antibodies harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. We identified 14 of 32 anti-spike MAbs that neutralised SARS-CoV-2 in independent assays at ≤ 133 nM (20 μg/ml) (five of 10 anti-RBD, three of 13 anti-non-RBD S1 subunit, six of nine anti-S2 subunit). Six of 10 anti-RBD MAbs showed evidence of blockade of ACE2 binding to RBD, and five of six of these were neutralising. Non-competing pairs of neutralising antibodies were identified, which offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.