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

Monir Ejemel, Qi Li, View ORCID ProfileShurong Hou, View ORCID ProfileZachary A. Schiller, View ORCID ProfileAaron L. Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Brianna J. Close, Da-Yuan Chen, Hasahn L. Conway, View ORCID ProfileSaeed Mohsan, Lisa A. Cavacini, Mark S. Klempner, View ORCID ProfileCelia A. Schiffer, Yang Wang
doi: https://doi.org/10.1101/2020.05.15.096719
Monir Ejemel
aMassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA
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Qi Li
aMassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA
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Shurong Hou
bBiochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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  • ORCID record for Shurong Hou
Zachary A. Schiller
aMassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA
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  • ORCID record for Zachary A. Schiller
Aaron L. Wallace
aMassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA
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  • ORCID record for Aaron L. Wallace
Alla Amcheslavsky
aMassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA
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Nese Kurt Yilmaz
bBiochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Jacqueline R. Toomey
aMassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA
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Ryan Schneider
aMassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA
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Brianna J. Close
aMassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA
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Da-Yuan Chen
cNational Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, USA
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Hasahn L. Conway
cNational Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, USA
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Saeed Mohsan
cNational Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, USA
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  • ORCID record for Saeed Mohsan
Lisa A. Cavacini
aMassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA
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  • For correspondence: yang.wang@umassmed.edu
Mark S. Klempner
aMassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA
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  • For correspondence: yang.wang@umassmed.edu
Celia A. Schiffer
bBiochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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  • ORCID record for Celia A. Schiffer
  • For correspondence: yang.wang@umassmed.edu
Yang Wang
aMassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA
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  • For correspondence: yang.wang@umassmed.edu
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Summary

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.

Competing Interest Statement

A patent application has been filed on 5 May 2020 on monoclonal antibodies targeting SARS-CoV-2 (U.S. Patent and Trademark Office patent application no. 63/020,483; patent applicants: Y.W., M.E., Q.L., and M.K., University of Massachusetts Medical School).

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Posted May 15, 2020.
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IgA MAb blocks SARS-CoV-2 Spike-ACE2 interaction providing mucosal immunity
Monir Ejemel, Qi Li, Shurong Hou, Zachary A. Schiller, Aaron L. Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Brianna J. Close, Da-Yuan Chen, Hasahn L. Conway, Saeed Mohsan, Lisa A. Cavacini, Mark S. Klempner, Celia A. Schiffer, Yang Wang
bioRxiv 2020.05.15.096719; doi: https://doi.org/10.1101/2020.05.15.096719
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IgA MAb blocks SARS-CoV-2 Spike-ACE2 interaction providing mucosal immunity
Monir Ejemel, Qi Li, Shurong Hou, Zachary A. Schiller, Aaron L. Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Brianna J. Close, Da-Yuan Chen, Hasahn L. Conway, Saeed Mohsan, Lisa A. Cavacini, Mark S. Klempner, Celia A. Schiffer, Yang Wang
bioRxiv 2020.05.15.096719; doi: https://doi.org/10.1101/2020.05.15.096719

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