Immunodominant Linear B-Cell Epitopes of SARS-CoV-2 Spike, Identified by Sera from K18-hACE2 Mice Infected with the WT or Variant Viruses

SARS-CoV-2 surface spike protein mediates the viral entry into the host cell and represents the primary immunological target of COVID-19 vaccines as well as post-exposure immunotherapy. Establishment of the highly immunogenic B-cell epitope profile of SARS-CoV-2 proteins in general, and that of the...

Full description

Bibliographic Details
Main Authors: Yinon Levy, Ron Alcalay, Anat Zvi, Efi Makdasi, Eldar Peretz, Tal Noy-Porat, Theodor Chitlaru, Michal Mandelboim, Ohad Mazor, Ronit Rosenfeld
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/10/2/251
_version_ 1797476163552018432
author Yinon Levy
Ron Alcalay
Anat Zvi
Efi Makdasi
Eldar Peretz
Tal Noy-Porat
Theodor Chitlaru
Michal Mandelboim
Ohad Mazor
Ronit Rosenfeld
author_facet Yinon Levy
Ron Alcalay
Anat Zvi
Efi Makdasi
Eldar Peretz
Tal Noy-Porat
Theodor Chitlaru
Michal Mandelboim
Ohad Mazor
Ronit Rosenfeld
author_sort Yinon Levy
collection DOAJ
description SARS-CoV-2 surface spike protein mediates the viral entry into the host cell and represents the primary immunological target of COVID-19 vaccines as well as post-exposure immunotherapy. Establishment of the highly immunogenic B-cell epitope profile of SARS-CoV-2 proteins in general, and that of the spike protein in particular, may contribute to the development of sensitive diagnostic tools and identification of vaccine` candidate targets. In the current study, the anti-viral antibody response in transgenic K18-hACE-2 mice was examined by implementing an immunodominant epitope mapping approach of the SARS-CoV-2 spike. Serum samples for probing an epitope array covering the entire spike protein were collected from mice following infection with the original SARS-CoV-2 strain as well as the B.1.1.7 Alpha and B.1.351 Beta genetic variants of concern. The analysis resulted in distinction of six linear epitopes common to the humoral response against all virus variants inspected at a frequency of more than 20% of the serum samples. Finally, the universality of the response was probed by cross-protective in vitro experiments using plaque-reducing neutralization tests. The data presented here has important implications for prediction of the efficacy of immune countermeasures against emerging SARS-CoV-2 variants.
first_indexed 2024-03-09T20:55:03Z
format Article
id doaj.art-f6d874276ff7471bb333a002d4ea3bbb
institution Directory Open Access Journal
issn 2076-393X
language English
last_indexed 2024-03-09T20:55:03Z
publishDate 2022-02-01
publisher MDPI AG
record_format Article
series Vaccines
spelling doaj.art-f6d874276ff7471bb333a002d4ea3bbb2023-11-23T22:26:02ZengMDPI AGVaccines2076-393X2022-02-0110225110.3390/vaccines10020251Immunodominant Linear B-Cell Epitopes of SARS-CoV-2 Spike, Identified by Sera from K18-hACE2 Mice Infected with the WT or Variant VirusesYinon Levy0Ron Alcalay1Anat Zvi2Efi Makdasi3Eldar Peretz4Tal Noy-Porat5Theodor Chitlaru6Michal Mandelboim7Ohad Mazor8Ronit Rosenfeld9Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 7410001, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 7410001, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 7410001, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 7410001, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 7410001, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 7410001, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 7410001, IsraelThe Central Virology Laboratory, Israel Ministry of Health, Tel Hashomer, Ramat Gan 5266202, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 7410001, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 7410001, IsraelSARS-CoV-2 surface spike protein mediates the viral entry into the host cell and represents the primary immunological target of COVID-19 vaccines as well as post-exposure immunotherapy. Establishment of the highly immunogenic B-cell epitope profile of SARS-CoV-2 proteins in general, and that of the spike protein in particular, may contribute to the development of sensitive diagnostic tools and identification of vaccine` candidate targets. In the current study, the anti-viral antibody response in transgenic K18-hACE-2 mice was examined by implementing an immunodominant epitope mapping approach of the SARS-CoV-2 spike. Serum samples for probing an epitope array covering the entire spike protein were collected from mice following infection with the original SARS-CoV-2 strain as well as the B.1.1.7 Alpha and B.1.351 Beta genetic variants of concern. The analysis resulted in distinction of six linear epitopes common to the humoral response against all virus variants inspected at a frequency of more than 20% of the serum samples. Finally, the universality of the response was probed by cross-protective in vitro experiments using plaque-reducing neutralization tests. The data presented here has important implications for prediction of the efficacy of immune countermeasures against emerging SARS-CoV-2 variants.https://www.mdpi.com/2076-393X/10/2/251COVID-19SARS-CoV-2epitope mappinglinear epitopesK18-hACE2
spellingShingle Yinon Levy
Ron Alcalay
Anat Zvi
Efi Makdasi
Eldar Peretz
Tal Noy-Porat
Theodor Chitlaru
Michal Mandelboim
Ohad Mazor
Ronit Rosenfeld
Immunodominant Linear B-Cell Epitopes of SARS-CoV-2 Spike, Identified by Sera from K18-hACE2 Mice Infected with the WT or Variant Viruses
Vaccines
COVID-19
SARS-CoV-2
epitope mapping
linear epitopes
K18-hACE2
title Immunodominant Linear B-Cell Epitopes of SARS-CoV-2 Spike, Identified by Sera from K18-hACE2 Mice Infected with the WT or Variant Viruses
title_full Immunodominant Linear B-Cell Epitopes of SARS-CoV-2 Spike, Identified by Sera from K18-hACE2 Mice Infected with the WT or Variant Viruses
title_fullStr Immunodominant Linear B-Cell Epitopes of SARS-CoV-2 Spike, Identified by Sera from K18-hACE2 Mice Infected with the WT or Variant Viruses
title_full_unstemmed Immunodominant Linear B-Cell Epitopes of SARS-CoV-2 Spike, Identified by Sera from K18-hACE2 Mice Infected with the WT or Variant Viruses
title_short Immunodominant Linear B-Cell Epitopes of SARS-CoV-2 Spike, Identified by Sera from K18-hACE2 Mice Infected with the WT or Variant Viruses
title_sort immunodominant linear b cell epitopes of sars cov 2 spike identified by sera from k18 hace2 mice infected with the wt or variant viruses
topic COVID-19
SARS-CoV-2
epitope mapping
linear epitopes
K18-hACE2
url https://www.mdpi.com/2076-393X/10/2/251
work_keys_str_mv AT yinonlevy immunodominantlinearbcellepitopesofsarscov2spikeidentifiedbyserafromk18hace2miceinfectedwiththewtorvariantviruses
AT ronalcalay immunodominantlinearbcellepitopesofsarscov2spikeidentifiedbyserafromk18hace2miceinfectedwiththewtorvariantviruses
AT anatzvi immunodominantlinearbcellepitopesofsarscov2spikeidentifiedbyserafromk18hace2miceinfectedwiththewtorvariantviruses
AT efimakdasi immunodominantlinearbcellepitopesofsarscov2spikeidentifiedbyserafromk18hace2miceinfectedwiththewtorvariantviruses
AT eldarperetz immunodominantlinearbcellepitopesofsarscov2spikeidentifiedbyserafromk18hace2miceinfectedwiththewtorvariantviruses
AT talnoyporat immunodominantlinearbcellepitopesofsarscov2spikeidentifiedbyserafromk18hace2miceinfectedwiththewtorvariantviruses
AT theodorchitlaru immunodominantlinearbcellepitopesofsarscov2spikeidentifiedbyserafromk18hace2miceinfectedwiththewtorvariantviruses
AT michalmandelboim immunodominantlinearbcellepitopesofsarscov2spikeidentifiedbyserafromk18hace2miceinfectedwiththewtorvariantviruses
AT ohadmazor immunodominantlinearbcellepitopesofsarscov2spikeidentifiedbyserafromk18hace2miceinfectedwiththewtorvariantviruses
AT ronitrosenfeld immunodominantlinearbcellepitopesofsarscov2spikeidentifiedbyserafromk18hace2miceinfectedwiththewtorvariantviruses