Cargando…
A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction
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 ch...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442812/ https://www.ncbi.nlm.nih.gov/pubmed/32826914 http://dx.doi.org/10.1038/s41467-020-18058-8 |
_version_ | 1783573509619843072 |
---|---|
author | 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 |
author_facet | 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 |
author_sort | Ejemel, Monir |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7442812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-74428122020-09-02 A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction 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 Nat Commun Article 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. Nature Publishing Group UK 2020-08-21 /pmc/articles/PMC7442812/ /pubmed/32826914 http://dx.doi.org/10.1038/s41467-020-18058-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article 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 A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction |
title | A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction |
title_full | A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction |
title_fullStr | A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction |
title_full_unstemmed | A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction |
title_short | A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction |
title_sort | cross-reactive human iga monoclonal antibody blocks sars-cov-2 spike-ace2 interaction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442812/ https://www.ncbi.nlm.nih.gov/pubmed/32826914 http://dx.doi.org/10.1038/s41467-020-18058-8 |
work_keys_str_mv | AT ejemelmonir acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT liqi acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT houshurong acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT schillerzacharya acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT treejuliaa acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT wallaceaaron acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT amcheslavskyalla acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT kurtyilmaznese acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT buttigiegkarenr acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT elmoremichaelj acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT godwinkerry acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT coombesnaomi acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT toomeyjacqueliner acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT schneiderryan acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT ramchettyanudeeps acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT closebriannaj acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT chendayuan acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT conwayhasahnl acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT saeedmohsan acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT ganesachandrashekar acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT carrollmilesw acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT cavacinilisaa acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT klempnermarks acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT schifferceliaa acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT wangyang acrossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT ejemelmonir crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT liqi crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT houshurong crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT schillerzacharya crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT treejuliaa crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT wallaceaaron crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT amcheslavskyalla crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT kurtyilmaznese crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT buttigiegkarenr crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT elmoremichaelj crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT godwinkerry crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT coombesnaomi crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT toomeyjacqueliner crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT schneiderryan crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT ramchettyanudeeps crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT closebriannaj crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT chendayuan crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT conwayhasahnl crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT saeedmohsan crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT ganesachandrashekar crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT carrollmilesw crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT cavacinilisaa crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT klempnermarks crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT schifferceliaa crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction AT wangyang crossreactivehumanigamonoclonalantibodyblockssarscov2spikeace2interaction |