A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy

Allison J. Greaney; Tyler N. Starr; Rachel T. Eguia; Andrea N. Loes; Khadija Khan; Farina Karim; Sandile Cele; John E. Bowen; Jennifer K. Logue; Davide Corti; David Veesler; Helen Y. Chu; Alex Sigal; Jesse D. Bloom

doi:10.1371/journal.ppat.1010248

A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy

Allison J. Greaney^*
, Tyler N. Starr
, Rachel T. Eguia
, Andrea N. Loes
, Khadija Khan
, Farina Karim
, Sandile Cele
, John E. Bowen
, Jennifer K. Logue
, Davide Corti
, David Veesler
, Helen Y. Chu
, Alex Sigal
, Jesse D. Bloom^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.

Original language	English
Article number	e1010248
Journal	PLoS Pathogens
Volume	18
Issue number	2
DOIs	https://doi.org/10.1371/journal.ppat.1010248
State	Published - Feb 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
Copyright: © 2022 Greaney et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1371/journal.ppat.1010248

Cite this

@article{dc41aa6762ec4882b20a130c268b8738,

title = "A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy",

abstract = "Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.",

author = "Greaney, \{Allison J.\} and Starr, \{Tyler N.\} and Eguia, \{Rachel T.\} and Loes, \{Andrea N.\} and Khadija Khan and Farina Karim and Sandile Cele and Bowen, \{John E.\} and Logue, \{Jennifer K.\} and Davide Corti and David Veesler and Chu, \{Helen Y.\} and Alex Sigal and Bloom, \{Jesse D.\}",

note = "Publisher Copyright: Copyright: {\textcopyright} 2022 Greaney et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2022",

month = feb,

doi = "10.1371/journal.ppat.1010248",

language = "אנגלית",

volume = "18",

journal = "PLoS Pathogens",

issn = "1553-7366",

publisher = "Public Library of Science",

number = "2",

}

TY - JOUR

T1 - A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy

AU - Greaney, Allison J.

AU - Starr, Tyler N.

AU - Eguia, Rachel T.

AU - Loes, Andrea N.

AU - Khan, Khadija

AU - Karim, Farina

AU - Cele, Sandile

AU - Bowen, John E.

AU - Logue, Jennifer K.

AU - Corti, Davide

AU - Veesler, David

AU - Chu, Helen Y.

AU - Sigal, Alex

AU - Bloom, Jesse D.

N1 - Publisher Copyright: Copyright: © 2022 Greaney et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2022/2

Y1 - 2022/2

N2 - Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.

AB - Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.

UR - https://www.scopus.com/pages/publications/85124480305

U2 - 10.1371/journal.ppat.1010248

DO - 10.1371/journal.ppat.1010248

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 35134084

AN - SCOPUS:85124480305

SN - 1553-7366

VL - 18

JO - PLoS Pathogens

JF - PLoS Pathogens

IS - 2

M1 - e1010248

ER -

A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this