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 Carroll; Lisa A. Cavacini; Mark S. Klempner; Celia A. Schiffer; Yang Wang

doi:10.1038/s41467-020-18058-8

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 GanesaMiles Carroll, Lisa A. Cavacini^*, Mark S. Klempner, Celia A. Schiffer, Yang Wang

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

114 Citations (Scopus)

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.

Original language	English
Article number	4198
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-18058-8
Publication status	Published - 1 Dec 2020

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Publisher Copyright:
© 2020, The Author(s).

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Ejemel, M., Li, Q., Hou, S., Schiller, Z. A., Tree, J. A., Wallace, A., Amcheslavsky, A., Kurt Yilmaz, N., Buttigieg, K. R., Elmore, M. J., Godwin, K., Coombes, N., Toomey, J. R., Schneider, R., Ramchetty, A. S., Close, B. J., Chen, D. Y., Conway, H. L., Saeed, M., ... Wang, Y. (2020). A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction. Nature Communications, 11(1), Article 4198. https://doi.org/10.1038/s41467-020-18058-8

@article{1acf296a682f4898bc89eb5913ad5fed,

title = "A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-18058-8",

language = "English",

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Ejemel, M, Li, Q, Hou, S, Schiller, ZA, Tree, JA, Wallace, A, Amcheslavsky, A, Kurt Yilmaz, N, Buttigieg, KR , Elmore, MJ , Godwin, K , Coombes, N, Toomey, JR, Schneider, R, Ramchetty, AS, Close, BJ, Chen, DY, Conway, HL, Saeed, M, Ganesa, C, Carroll, M, Cavacini, LA, Klempner, MS, Schiffer, CA & Wang, Y 2020, 'A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction', Nature Communications, vol. 11, no. 1, 4198. https://doi.org/10.1038/s41467-020-18058-8

TY - JOUR

T1 - A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction

AU - Ejemel, Monir

AU - Li, Qi

AU - Hou, Shurong

AU - Schiller, Zachary A.

AU - Tree, Julia A.

AU - Wallace, Aaron

AU - Amcheslavsky, Alla

AU - Kurt Yilmaz, Nese

AU - Buttigieg, Karen R.

AU - Elmore, Michael J.

AU - Godwin, Kerry

AU - Coombes, Naomi

AU - Toomey, Jacqueline R.

AU - Schneider, Ryan

AU - Ramchetty, Anudeep S.

AU - Close, Brianna J.

AU - Chen, Da Yuan

AU - Conway, Hasahn L.

AU - Saeed, Mohsan

AU - Ganesa, Chandrashekar

AU - Carroll, Miles

AU - Cavacini, Lisa A.

AU - Klempner, Mark S.

AU - Schiffer, Celia A.

AU - Wang, Yang

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-020-18058-8

DO - 10.1038/s41467-020-18058-8

M3 - Article

C2 - 32826914

AN - SCOPUS:85089677225

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4198

ER -

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

Abstract

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