A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction.
Ejemel M., Li Q., Hou S., Schiller ZA., Tree JA., Wallace A., Amcheslavsky A., Kurt Yilmaz N., Buttigieg KR., Elmore MJ., Godwin K., Coombes N., Toomey JR., Schneider R., Ramchetty AS., Close BJ., Chen D-Y., Conway HL., Saeed M., Ganesa C., Carroll MW., Cavacini LA., Klempner MS., Schiffer CA., Wang Y.
COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 virus while the IgG isotype shows no neutralization. Our results suggest that SARS-CoV-2 specific IgA antibodies, such as MAb362, may provide effective immunity against SARS-CoV-2 by inducing mucosal immunity within the respiratory system, a potentially critical feature of an effective vaccine.