IgA MAb blocks SARS-CoV-2 Spike-ACE2 interaction providing mucosal immunity

Ejemel, Monir; Li, Qi; Hou, Shurong; Schiller, Zachary A.; Wallace, Aaron L.; Amcheslavsky, Alla; Yilmaz, Nese Kurt; Toomey, Jacqueline R.; Schneider, Ryan; Close, Brianna J.; Chen, Da-Yuan; Conway, Hasahn L.; Mohsan, Saeed; 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 hACE2 receptor binding, by completely overlapping the hACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in human epithelial cells expressing hACE2. 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.