A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction

Ejemel, Monir; Li, Qi; Hou, Shurong; Schiller, Zachary A.; Tree, Julia A.; Wallace, Aaron; Amcheslavsky, Alla; Kurt Yilmaz, Nese; Buttigieg, Karen R.; Elmore, Michael J.; Godwin, Kerry; Coombes, Naomi; Toomey, Jacqueline R.; Schneider, Ryan; Ramchetty, Anudeep S.; Close, Brianna J.; Chen, Da-Yuan; Conway, Hasahn L.; Saeed, Mohsan; Ganesa, Chandrashekar; Carroll, Miles W.; Cavacini, Lisa A.; Klempner, Mark S.; Schiffer, Celia A.; Wang, Yang

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.