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SARS-CoV-2 variants with reduced infectivity and varied sensitivity to the BNT162b2 vaccine are developed during the course of infection

In-depth analysis of SARS-CoV-2 quasispecies is pivotal for a thorough understating of its evolution during infection. The recent deployment of COVID-19 vaccines, which elicit protective anti-spike neutralizing antibodies, has stressed the importance of uncovering and characterizing SARS-CoV-2 varia...

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Autores principales: Khateeb, Dina, Gabrieli, Tslil, Sofer, Bar, Hattar, Adi, Cordela, Sapir, Chaouat, Abigael, Spivak, Ilia, Lejbkowicz, Izabella, Almog, Ronit, Mandelboim, Michal, Bar-On, Yotam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789181/
https://www.ncbi.nlm.nih.gov/pubmed/35020754
http://dx.doi.org/10.1371/journal.ppat.1010242
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author Khateeb, Dina
Gabrieli, Tslil
Sofer, Bar
Hattar, Adi
Cordela, Sapir
Chaouat, Abigael
Spivak, Ilia
Lejbkowicz, Izabella
Almog, Ronit
Mandelboim, Michal
Bar-On, Yotam
author_facet Khateeb, Dina
Gabrieli, Tslil
Sofer, Bar
Hattar, Adi
Cordela, Sapir
Chaouat, Abigael
Spivak, Ilia
Lejbkowicz, Izabella
Almog, Ronit
Mandelboim, Michal
Bar-On, Yotam
author_sort Khateeb, Dina
collection PubMed
description In-depth analysis of SARS-CoV-2 quasispecies is pivotal for a thorough understating of its evolution during infection. The recent deployment of COVID-19 vaccines, which elicit protective anti-spike neutralizing antibodies, has stressed the importance of uncovering and characterizing SARS-CoV-2 variants with mutated spike proteins. Sequencing databases have allowed to follow the spread of SARS-CoV-2 variants that are circulating in the human population, and several experimental platforms were developed to study these variants. However, less is known about the SARS-CoV-2 variants that are developed in the respiratory system of the infected individual. To gain further insight on SARS-CoV-2 mutagenesis during natural infection, we preformed single-genome sequencing of SARS-CoV-2 isolated from nose-throat swabs of infected individuals. Interestingly, intra-host SARS-CoV-2 variants with mutated S genes or N genes were detected in all individuals who were analyzed. These intra-host variants were present in low frequencies in the swab samples and were rarely documented in current sequencing databases. Further examination of representative spike variants identified by our analysis showed that these variants have impaired infectivity capacity and that the mutated variants showed varied sensitivity to neutralization by convalescent plasma and to plasma from vaccinated individuals. Notably, analysis of the plasma neutralization activity against these variants showed that the L1197I mutation at the S2 subunit of the spike can affect the plasma neutralization activity. Together, these results suggest that SARS-CoV-2 intra-host variants should be further analyzed for a more thorough characterization of potential circulating variants.
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spelling pubmed-87891812022-01-26 SARS-CoV-2 variants with reduced infectivity and varied sensitivity to the BNT162b2 vaccine are developed during the course of infection Khateeb, Dina Gabrieli, Tslil Sofer, Bar Hattar, Adi Cordela, Sapir Chaouat, Abigael Spivak, Ilia Lejbkowicz, Izabella Almog, Ronit Mandelboim, Michal Bar-On, Yotam PLoS Pathog Research Article In-depth analysis of SARS-CoV-2 quasispecies is pivotal for a thorough understating of its evolution during infection. The recent deployment of COVID-19 vaccines, which elicit protective anti-spike neutralizing antibodies, has stressed the importance of uncovering and characterizing SARS-CoV-2 variants with mutated spike proteins. Sequencing databases have allowed to follow the spread of SARS-CoV-2 variants that are circulating in the human population, and several experimental platforms were developed to study these variants. However, less is known about the SARS-CoV-2 variants that are developed in the respiratory system of the infected individual. To gain further insight on SARS-CoV-2 mutagenesis during natural infection, we preformed single-genome sequencing of SARS-CoV-2 isolated from nose-throat swabs of infected individuals. Interestingly, intra-host SARS-CoV-2 variants with mutated S genes or N genes were detected in all individuals who were analyzed. These intra-host variants were present in low frequencies in the swab samples and were rarely documented in current sequencing databases. Further examination of representative spike variants identified by our analysis showed that these variants have impaired infectivity capacity and that the mutated variants showed varied sensitivity to neutralization by convalescent plasma and to plasma from vaccinated individuals. Notably, analysis of the plasma neutralization activity against these variants showed that the L1197I mutation at the S2 subunit of the spike can affect the plasma neutralization activity. Together, these results suggest that SARS-CoV-2 intra-host variants should be further analyzed for a more thorough characterization of potential circulating variants. Public Library of Science 2022-01-12 /pmc/articles/PMC8789181/ /pubmed/35020754 http://dx.doi.org/10.1371/journal.ppat.1010242 Text en © 2022 Khateeb et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Khateeb, Dina
Gabrieli, Tslil
Sofer, Bar
Hattar, Adi
Cordela, Sapir
Chaouat, Abigael
Spivak, Ilia
Lejbkowicz, Izabella
Almog, Ronit
Mandelboim, Michal
Bar-On, Yotam
SARS-CoV-2 variants with reduced infectivity and varied sensitivity to the BNT162b2 vaccine are developed during the course of infection
title SARS-CoV-2 variants with reduced infectivity and varied sensitivity to the BNT162b2 vaccine are developed during the course of infection
title_full SARS-CoV-2 variants with reduced infectivity and varied sensitivity to the BNT162b2 vaccine are developed during the course of infection
title_fullStr SARS-CoV-2 variants with reduced infectivity and varied sensitivity to the BNT162b2 vaccine are developed during the course of infection
title_full_unstemmed SARS-CoV-2 variants with reduced infectivity and varied sensitivity to the BNT162b2 vaccine are developed during the course of infection
title_short SARS-CoV-2 variants with reduced infectivity and varied sensitivity to the BNT162b2 vaccine are developed during the course of infection
title_sort sars-cov-2 variants with reduced infectivity and varied sensitivity to the bnt162b2 vaccine are developed during the course of infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789181/
https://www.ncbi.nlm.nih.gov/pubmed/35020754
http://dx.doi.org/10.1371/journal.ppat.1010242
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