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

• Published in: Nature communications Vol. 11; no. 1; p. 4198
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 21.08.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: ACE2; Angiotensin-Converting Enzyme 2; Animals; Antibodies; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - metabolism; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - metabolism; Betacoronavirus - immunology; Binding; Chlorocebus aethiops; COVID-19; Cross Reactions; Epitopes; HEK293 Cells; Humans; Immunity; Immunoglobulin A; Immunoglobulin A - immunology; Immunoglobulin A - metabolism; Immunoglobulin A, Secretory - immunology; Immunoglobulin A, Secretory - metabolism; Immunoglobulin G; Immunoglobulin G - immunology; Immunoglobulin G - metabolism; Models, Molecular; Monoclonal antibodies; Morbidity; Mucosal immunity; Mutation; Neutralization; Pandemics; Peptidyl-Dipeptidase A - metabolism; Protein Binding; Protein Interaction Domains and Motifs; Receptors; Respiratory system; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Severe acute respiratory syndrome-related coronavirus - immunology; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Vaccines; Vero Cells; Viral diseases; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-18058-8

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.