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

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

doi:10.1038/s41467-020-18058-8

Monir Ejemel, Aaron Wallace + Show 23 more

Open Access

https://doi.org/10.1038/s41467-020-18058-8

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Abstract

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.

Highlights

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
We have previously developed and characterized a panel of human monoclonal antibodies (MAbs) that targets the receptor-binding domain (RBD) of the SARS-CoV S glycoprotein, isolated from transgenic mice expressing human immunoglobulin genes[9,10]
MAb362 was identified with cross-binding activity against both the RBD and S1 subunit of the SARS-CoV and SARS-CoV-2 spike proteins (Supplementary Table 1)

Summary

Introduction

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. The feasibility of human monoclonal antibodies (MAbs) as immunoprophylaxis or therapy against coronaviruses including SARSCoV7–10 and MERS-CoV11 has been demonstrated These anticoronavirus MAbs primarily target the viral spike (S) glycoprotein, a type I transmembrane glycoprotein that produces recognizable crown-like spike structures on the virus surface. Most current anti-SARS-CoV MAbs neutralize virus by binding to epitopes on the spike protein RBD of SARS-CoV15. We and others have demonstrated that neutralizing MAbs that block RBD-ACE2 binding could confer potent protection against SARS-CoV as both prophylaxis and treatment in various animal models[7,9,10]. Antibody-dependent enhancement of viral infections are one of the major hurdles in the development of effective vaccines This enhancement is likely facilitated by the Fc domain of IgG but not for its isotype variant IgA18. How precisely which isotype may protect the mucosa from SARSCoV-2 infection remains an open question

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