Cargando…

Antibody-Mediated Neutralization of Authentic SARS-CoV-2 B.1.617 Variants Harboring L452R and T478K/E484Q

The capacity of convalescent and vaccine-elicited sera and monoclonal antibodies (mAb) to neutralize SARS-CoV-2 variants is currently of high relevance to assess the protection against infections. We performed a cell culture-based neutralization assay focusing on authentic SARS-CoV-2 variants B.1.61...

Descripción completa

Detalles Bibliográficos
Autores principales: Wilhelm, Alexander, Toptan, Tuna, Pallas, Christiane, Wolf, Timo, Goetsch, Udo, Gottschalk, Rene, Vehreschild, Maria J. G. T., Ciesek, Sandra, Widera, Marek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473269/
https://www.ncbi.nlm.nih.gov/pubmed/34578275
http://dx.doi.org/10.3390/v13091693
_version_ 1784574949727404032
author Wilhelm, Alexander
Toptan, Tuna
Pallas, Christiane
Wolf, Timo
Goetsch, Udo
Gottschalk, Rene
Vehreschild, Maria J. G. T.
Ciesek, Sandra
Widera, Marek
author_facet Wilhelm, Alexander
Toptan, Tuna
Pallas, Christiane
Wolf, Timo
Goetsch, Udo
Gottschalk, Rene
Vehreschild, Maria J. G. T.
Ciesek, Sandra
Widera, Marek
author_sort Wilhelm, Alexander
collection PubMed
description The capacity of convalescent and vaccine-elicited sera and monoclonal antibodies (mAb) to neutralize SARS-CoV-2 variants is currently of high relevance to assess the protection against infections. We performed a cell culture-based neutralization assay focusing on authentic SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.427/B.1.429 (Epsilon), all harboring the spike substitution L452R. We found that authentic SARS-CoV-2 variants harboring L452R had reduced susceptibility to convalescent and vaccine-elicited sera and mAbs. Compared to B.1, Kappa and Delta showed a reduced neutralization by convalescent sera by a factor of 8.00 and 5.33, respectively, which constitutes a 2-fold greater reduction when compared to Epsilon. BNT2b2 and mRNA1273 vaccine-elicited sera were less effective against Kappa, Delta, and Epsilon compared to B.1. No difference was observed between Kappa and Delta towards vaccine-elicited sera, whereas convalescent sera were 1.51-fold less effective against Delta, respectively. Both B.1.617 variants Kappa (+E484Q) and Delta (+T478K) were less susceptible to either casirivimab or imdevimab. In conclusion, in contrast to the parallel circulating Kappa variant, the neutralization efficiency of convalescent and vaccine-elicited sera against Delta was moderately reduced. Delta was resistant to imdevimab, which, however, might be circumvented by combination therapy with casirivimab together.
format Online
Article
Text
id pubmed-8473269
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-84732692021-09-28 Antibody-Mediated Neutralization of Authentic SARS-CoV-2 B.1.617 Variants Harboring L452R and T478K/E484Q Wilhelm, Alexander Toptan, Tuna Pallas, Christiane Wolf, Timo Goetsch, Udo Gottschalk, Rene Vehreschild, Maria J. G. T. Ciesek, Sandra Widera, Marek Viruses Communication The capacity of convalescent and vaccine-elicited sera and monoclonal antibodies (mAb) to neutralize SARS-CoV-2 variants is currently of high relevance to assess the protection against infections. We performed a cell culture-based neutralization assay focusing on authentic SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.427/B.1.429 (Epsilon), all harboring the spike substitution L452R. We found that authentic SARS-CoV-2 variants harboring L452R had reduced susceptibility to convalescent and vaccine-elicited sera and mAbs. Compared to B.1, Kappa and Delta showed a reduced neutralization by convalescent sera by a factor of 8.00 and 5.33, respectively, which constitutes a 2-fold greater reduction when compared to Epsilon. BNT2b2 and mRNA1273 vaccine-elicited sera were less effective against Kappa, Delta, and Epsilon compared to B.1. No difference was observed between Kappa and Delta towards vaccine-elicited sera, whereas convalescent sera were 1.51-fold less effective against Delta, respectively. Both B.1.617 variants Kappa (+E484Q) and Delta (+T478K) were less susceptible to either casirivimab or imdevimab. In conclusion, in contrast to the parallel circulating Kappa variant, the neutralization efficiency of convalescent and vaccine-elicited sera against Delta was moderately reduced. Delta was resistant to imdevimab, which, however, might be circumvented by combination therapy with casirivimab together. MDPI 2021-08-26 /pmc/articles/PMC8473269/ /pubmed/34578275 http://dx.doi.org/10.3390/v13091693 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Wilhelm, Alexander
Toptan, Tuna
Pallas, Christiane
Wolf, Timo
Goetsch, Udo
Gottschalk, Rene
Vehreschild, Maria J. G. T.
Ciesek, Sandra
Widera, Marek
Antibody-Mediated Neutralization of Authentic SARS-CoV-2 B.1.617 Variants Harboring L452R and T478K/E484Q
title Antibody-Mediated Neutralization of Authentic SARS-CoV-2 B.1.617 Variants Harboring L452R and T478K/E484Q
title_full Antibody-Mediated Neutralization of Authentic SARS-CoV-2 B.1.617 Variants Harboring L452R and T478K/E484Q
title_fullStr Antibody-Mediated Neutralization of Authentic SARS-CoV-2 B.1.617 Variants Harboring L452R and T478K/E484Q
title_full_unstemmed Antibody-Mediated Neutralization of Authentic SARS-CoV-2 B.1.617 Variants Harboring L452R and T478K/E484Q
title_short Antibody-Mediated Neutralization of Authentic SARS-CoV-2 B.1.617 Variants Harboring L452R and T478K/E484Q
title_sort antibody-mediated neutralization of authentic sars-cov-2 b.1.617 variants harboring l452r and t478k/e484q
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473269/
https://www.ncbi.nlm.nih.gov/pubmed/34578275
http://dx.doi.org/10.3390/v13091693
work_keys_str_mv AT wilhelmalexander antibodymediatedneutralizationofauthenticsarscov2b1617variantsharboringl452randt478ke484q
AT toptantuna antibodymediatedneutralizationofauthenticsarscov2b1617variantsharboringl452randt478ke484q
AT pallaschristiane antibodymediatedneutralizationofauthenticsarscov2b1617variantsharboringl452randt478ke484q
AT wolftimo antibodymediatedneutralizationofauthenticsarscov2b1617variantsharboringl452randt478ke484q
AT goetschudo antibodymediatedneutralizationofauthenticsarscov2b1617variantsharboringl452randt478ke484q
AT gottschalkrene antibodymediatedneutralizationofauthenticsarscov2b1617variantsharboringl452randt478ke484q
AT vehreschildmariajgt antibodymediatedneutralizationofauthenticsarscov2b1617variantsharboringl452randt478ke484q
AT cieseksandra antibodymediatedneutralizationofauthenticsarscov2b1617variantsharboringl452randt478ke484q
AT wideramarek antibodymediatedneutralizationofauthenticsarscov2b1617variantsharboringl452randt478ke484q