Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zekri, Latifa, Ruetalo, Natalia, Christie, Mary, Walker, Carolin, Manz, Timo, Rammensee, Hans-Georg, Salih, Helmut R., Schindler, Michael, Jung, Gundram
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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
_version_ 1784910492776529920
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
title_full Novel ACE2 fusion protein with adapting activity against SARS-CoV-2 variants in vitro
title_fullStr Novel ACE2 fusion protein with adapting activity against SARS-CoV-2 variants in vitro
title_full_unstemmed Novel ACE2 fusion protein with adapting activity against SARS-CoV-2 variants in vitro
title_short Novel ACE2 fusion protein with adapting activity against SARS-CoV-2 variants in vitro
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
work_keys_str_mv AT zekrilatifa novelace2fusionproteinwithadaptingactivityagainstsarscov2variantsinvitro
AT ruetalonatalia novelace2fusionproteinwithadaptingactivityagainstsarscov2variantsinvitro
AT christiemary novelace2fusionproteinwithadaptingactivityagainstsarscov2variantsinvitro
AT walkercarolin novelace2fusionproteinwithadaptingactivityagainstsarscov2variantsinvitro
AT manztimo novelace2fusionproteinwithadaptingactivityagainstsarscov2variantsinvitro
AT rammenseehansgeorg novelace2fusionproteinwithadaptingactivityagainstsarscov2variantsinvitro
AT salihhelmutr novelace2fusionproteinwithadaptingactivityagainstsarscov2variantsinvitro
AT schindlermichael novelace2fusionproteinwithadaptingactivityagainstsarscov2variantsinvitro
AT junggundram novelace2fusionproteinwithadaptingactivityagainstsarscov2variantsinvitro