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Novel ACE2 fusion protein with adapting activity against SARS-CoV-2 variants in vitro
Despite the successful development of vaccines and neutralizing antibodies to limit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerging variants prolong the pandemic and emphasize the persistent need to develop effective antiviral treatment regimens. Recombinant anti...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030959/ https://www.ncbi.nlm.nih.gov/pubmed/36969164 http://dx.doi.org/10.3389/fimmu.2023.1112505 |
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author | Zekri, Latifa Ruetalo, Natalia Christie, Mary Walker, Carolin Manz, Timo Rammensee, Hans-Georg Salih, Helmut R. Schindler, Michael Jung, Gundram |
author_facet | Zekri, Latifa Ruetalo, Natalia Christie, Mary Walker, Carolin Manz, Timo Rammensee, Hans-Georg Salih, Helmut R. Schindler, Michael Jung, Gundram |
author_sort | Zekri, Latifa |
collection | PubMed |
description | Despite the successful development of vaccines and neutralizing antibodies to limit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerging variants prolong the pandemic and emphasize the persistent need to develop effective antiviral treatment regimens. Recombinant antibodies directed to the original SARS-CoV-2 have been successfully used to treat established viral disease. However, emerging viral variants escape the recognition by those antibodies. Here we report the engineering of an optimized ACE2 fusion protein, designated ACE2-M, which comprises a human IgG1 Fc domain with abrogated Fc-receptor binding linked to a catalytically-inactive ACE2 extracellular domain that displays increased apparent affinity to the B.1 spike protein. The affinity and neutralization capacity of ACE2-M is unaffected or even enhanced by mutations present in the spike protein of viral variants. In contrast, a recombinant neutralizing reference antibody, as well as antibodies present in the sera of vaccinated individuals, lose activity against such variants. With its potential to resist viral immune escape ACE2-M appears to be particularly valuable in the context of pandemic preparedness towards newly emerging coronaviruses. |
format | Online Article Text |
id | pubmed-10030959 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100309592023-03-23 Novel ACE2 fusion protein with adapting activity against SARS-CoV-2 variants in vitro Zekri, Latifa Ruetalo, Natalia Christie, Mary Walker, Carolin Manz, Timo Rammensee, Hans-Georg Salih, Helmut R. Schindler, Michael Jung, Gundram Front Immunol Immunology Despite the successful development of vaccines and neutralizing antibodies to limit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerging variants prolong the pandemic and emphasize the persistent need to develop effective antiviral treatment regimens. Recombinant antibodies directed to the original SARS-CoV-2 have been successfully used to treat established viral disease. However, emerging viral variants escape the recognition by those antibodies. Here we report the engineering of an optimized ACE2 fusion protein, designated ACE2-M, which comprises a human IgG1 Fc domain with abrogated Fc-receptor binding linked to a catalytically-inactive ACE2 extracellular domain that displays increased apparent affinity to the B.1 spike protein. The affinity and neutralization capacity of ACE2-M is unaffected or even enhanced by mutations present in the spike protein of viral variants. In contrast, a recombinant neutralizing reference antibody, as well as antibodies present in the sera of vaccinated individuals, lose activity against such variants. With its potential to resist viral immune escape ACE2-M appears to be particularly valuable in the context of pandemic preparedness towards newly emerging coronaviruses. Frontiers Media S.A. 2023-03-08 /pmc/articles/PMC10030959/ /pubmed/36969164 http://dx.doi.org/10.3389/fimmu.2023.1112505 Text en Copyright © 2023 Zekri, Ruetalo, Christie, Walker, Manz, Rammensee, Salih, Schindler and Jung https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Zekri, Latifa Ruetalo, Natalia Christie, Mary Walker, Carolin Manz, Timo Rammensee, Hans-Georg Salih, Helmut R. Schindler, Michael Jung, Gundram Novel ACE2 fusion protein with adapting activity against SARS-CoV-2 variants in vitro |
title | Novel ACE2 fusion protein with adapting activity against SARS-CoV-2 variants in vitro
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title_full | Novel ACE2 fusion protein with adapting activity against SARS-CoV-2 variants in vitro
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title_fullStr | Novel ACE2 fusion protein with adapting activity against SARS-CoV-2 variants in vitro
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title_full_unstemmed | Novel ACE2 fusion protein with adapting activity against SARS-CoV-2 variants in vitro
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title_short | Novel ACE2 fusion protein with adapting activity against SARS-CoV-2 variants in vitro
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title_sort | novel ace2 fusion protein with adapting activity against sars-cov-2 variants in vitro |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030959/ https://www.ncbi.nlm.nih.gov/pubmed/36969164 http://dx.doi.org/10.3389/fimmu.2023.1112505 |
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