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

Monir Ejemel, Qi Li, Shurong Hou, Zachary A. Schiller, Julia A. Tree, Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Karen R. Buttigieg, Michael J. Elmore, Kerry Godwin, Naomi Coombes, Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty, Brianna J. Close, Da-Yuan Chen, Hasahn L. Conway, Mohsan Saeed, Chandrashekar Ganesa, Miles W. Carroll, Lisa A. Cavacini (), Mark S. Klempner (), Celia A. Schiffer () and Yang Wang ()
Additional contact information
Monir Ejemel: MassBiologics of the University of Massachusetts Medical School
Qi Li: MassBiologics of the University of Massachusetts Medical School
Shurong Hou: University of Massachusetts Medical School
Zachary A. Schiller: MassBiologics of the University of Massachusetts Medical School
Julia A. Tree: Public Health England, Porton Down
Aaron Wallace: MassBiologics of the University of Massachusetts Medical School
Alla Amcheslavsky: MassBiologics of the University of Massachusetts Medical School
Nese Kurt Yilmaz: University of Massachusetts Medical School
Karen R. Buttigieg: Public Health England, Porton Down
Michael J. Elmore: Public Health England, Porton Down
Kerry Godwin: Public Health England, Porton Down
Naomi Coombes: Public Health England, Porton Down
Jacqueline R. Toomey: MassBiologics of the University of Massachusetts Medical School
Ryan Schneider: MassBiologics of the University of Massachusetts Medical School
Anudeep S. Ramchetty: MassBiologics of the University of Massachusetts Medical School
Brianna J. Close: Boston University
Da-Yuan Chen: Boston University
Hasahn L. Conway: Boston University
Mohsan Saeed: Boston University
Chandrashekar Ganesa: MassBiologics of the University of Massachusetts Medical School
Miles W. Carroll: Public Health England, Porton Down
Lisa A. Cavacini: MassBiologics of the University of Massachusetts Medical School
Mark S. Klempner: MassBiologics of the University of Massachusetts Medical School
Celia A. Schiffer: University of Massachusetts Medical School
Yang Wang: MassBiologics of the University of Massachusetts Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18058-8

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