Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes

Chunyan Wang; Emma L Hesketh; Tatiana M Shamorkina; Wentao Li; Peter J Franken; Dubravka Drabek; Rien van Haperen; Sarah Townend; Frank J M van Kuppeveld; Frank Grosveld; Neil A Ranson; Joost Snijder; Raoul J de Groot; Daniel L Hurdiss; Berend-Jan Bosch

doi:10.1038/s41467-022-30658-0

Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes

Chunyan Wang, Emma L Hesketh, Tatiana M Shamorkina, Wentao Li, Peter J Franken, Dubravka Drabek, Rien van Haperen, Sarah Townend, Frank J M van Kuppeveld, Frank Grosveld, Neil A Ranson, Joost Snijder, Raoul J de Groot, Daniel L Hurdiss^*, Berend-Jan Bosch^*

^*Corresponding author for this work

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

Abstract

Human coronavirus OC43 is a globally circulating common cold virus sustained by recurrent reinfections. How it persists in the population and defies existing herd immunity is unknown. Here we focus on viral glycoprotein S, the target for neutralizing antibodies, and provide an in-depth analysis of its antigenic structure. Neutralizing antibodies are directed to the sialoglycan-receptor binding site in S1 A domain, but, remarkably, also to S1 B. The latter block infection yet do not prevent sialoglycan binding. While two distinct neutralizing S1 B epitopes are readily accessible in the prefusion S trimer, other sites are occluded such that their accessibility must be subject to conformational changes in S during cell-entry. While non-neutralizing antibodies were broadly reactive against a collection of natural OC43 variants, neutralizing antibodies generally displayed restricted binding breadth. Our data provide a structure-based understanding of protective immunity and adaptive evolution for this endemic coronavirus which emerged in humans long before SARS-CoV-2.

Original language	English
Article number	2921
Pages (from-to)	1-15
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-30658-0
Publication status	Published - Dec 2022

Bibliographical note

Funding Information:
We thank Tony Smits for technical support. This study was done within the framework of the Utrecht Molecular Immunology Hub - Utrecht University and the research programme of the Netherlands Centre for One Health (www.ncoh.nl). Funding: The collaboration project is co-funded by the PPP Allowance made available by Health~Holland (Grant no. LSHM19136), Top Sector Life Sciences & Health, to stimulate public-private partnerships. Chunyan Wang was supported by a grant from the China Scholarship Council. T.M.S. and J.S. were funded by the Dutch Research Council NWO Gravitation 2013 BOO, Institute for Chemical Immunology (ICI; 024.002.009). Cryo-EM data processing was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative using grant no. EINF-398.

Funding Information:
We thank Tony Smits for technical support. This study was done within the framework of the Utrecht Molecular Immunology Hub - Utrecht University and the research programme of the Netherlands Centre for One Health ( www.ncoh.nl ). Funding: The collaboration project is co-funded by the PPP Allowance made available by Health~Holland (Grant no. LSHM19136), Top Sector Life Sciences & Health, to stimulate public-private partnerships. Chunyan Wang was supported by a grant from the China Scholarship Council. T.M.S. and J.S. were funded by the Dutch Research Council NWO Gravitation 2013 BOO, Institute for Chemical Immunology (ICI; 024.002.009). Cryo-EM data processing was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative using grant no. EINF-398.

Publisher Copyright:
© 2022, The Author(s).

Keywords

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
COVID-19
Coronavirus OC43, Human/metabolism
Epitopes
Humans
SARS-CoV-2
Spike Glycoprotein, Coronavirus

Access to Document

10.1038/s41467-022-30658-0Licence: CC BY

s41467-022-30658-0Final published version, 5.21 MBLicence: CC BY

Cite this

Wang, C., Hesketh, E. L., Shamorkina, T. M., Li, W., Franken, P. J., Drabek, D., van Haperen, R., Townend, S., van Kuppeveld, F. J. M., Grosveld, F., Ranson, N. A., Snijder, J., de Groot, R. J., Hurdiss, D. L., & Bosch, B.-J. (2022). Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes. Nature Communications, 13(1), 1-15. Article 2921. https://doi.org/10.1038/s41467-022-30658-0

@article{884037f214c04899abed755f1f04a511,

title = "Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes",

abstract = "Human coronavirus OC43 is a globally circulating common cold virus sustained by recurrent reinfections. How it persists in the population and defies existing herd immunity is unknown. Here we focus on viral glycoprotein S, the target for neutralizing antibodies, and provide an in-depth analysis of its antigenic structure. Neutralizing antibodies are directed to the sialoglycan-receptor binding site in S1 A domain, but, remarkably, also to S1 B. The latter block infection yet do not prevent sialoglycan binding. While two distinct neutralizing S1 B epitopes are readily accessible in the prefusion S trimer, other sites are occluded such that their accessibility must be subject to conformational changes in S during cell-entry. While non-neutralizing antibodies were broadly reactive against a collection of natural OC43 variants, neutralizing antibodies generally displayed restricted binding breadth. Our data provide a structure-based understanding of protective immunity and adaptive evolution for this endemic coronavirus which emerged in humans long before SARS-CoV-2. ",

keywords = "Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, Coronavirus OC43, Human/metabolism, Epitopes, Humans, SARS-CoV-2, Spike Glycoprotein, Coronavirus",

author = "Chunyan Wang and Hesketh, {Emma L} and Shamorkina, {Tatiana M} and Wentao Li and Franken, {Peter J} and Dubravka Drabek and {van Haperen}, Rien and Sarah Townend and {van Kuppeveld}, {Frank J M} and Frank Grosveld and Ranson, {Neil A} and Joost Snijder and {de Groot}, {Raoul J} and Hurdiss, {Daniel L} and Berend-Jan Bosch",

note = "Funding Information: We thank Tony Smits for technical support. This study was done within the framework of the Utrecht Molecular Immunology Hub - Utrecht University and the research programme of the Netherlands Centre for One Health (www.ncoh.nl). Funding: The collaboration project is co-funded by the PPP Allowance made available by Health~Holland (Grant no. LSHM19136), Top Sector Life Sciences & Health, to stimulate public-private partnerships. Chunyan Wang was supported by a grant from the China Scholarship Council. T.M.S. and J.S. were funded by the Dutch Research Council NWO Gravitation 2013 BOO, Institute for Chemical Immunology (ICI; 024.002.009). Cryo-EM data processing was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative using grant no. EINF-398. Funding Information: We thank Tony Smits for technical support. This study was done within the framework of the Utrecht Molecular Immunology Hub - Utrecht University and the research programme of the Netherlands Centre for One Health ( www.ncoh.nl ). Funding: The collaboration project is co-funded by the PPP Allowance made available by Health~Holland (Grant no. LSHM19136), Top Sector Life Sciences & Health, to stimulate public-private partnerships. Chunyan Wang was supported by a grant from the China Scholarship Council. T.M.S. and J.S. were funded by the Dutch Research Council NWO Gravitation 2013 BOO, Institute for Chemical Immunology (ICI; 024.002.009). Cryo-EM data processing was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative using grant no. EINF-398. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-30658-0",

language = "English",

volume = "13",

pages = "1--15",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Wang, C, Hesketh, EL, Shamorkina, TM, Li, W, Franken, PJ, Drabek, D, van Haperen, R, Townend, S, van Kuppeveld, FJM, Grosveld, F, Ranson, NA, Snijder, J , de Groot, RJ , Hurdiss, DL & Bosch, B-J 2022, 'Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes', Nature Communications, vol. 13, no. 1, 2921, pp. 1-15. https://doi.org/10.1038/s41467-022-30658-0

TY - JOUR

T1 - Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes

AU - Wang, Chunyan

AU - Hesketh, Emma L

AU - Shamorkina, Tatiana M

AU - Li, Wentao

AU - Franken, Peter J

AU - Drabek, Dubravka

AU - van Haperen, Rien

AU - Townend, Sarah

AU - van Kuppeveld, Frank J M

AU - Grosveld, Frank

AU - Ranson, Neil A

AU - Snijder, Joost

AU - de Groot, Raoul J

AU - Hurdiss, Daniel L

AU - Bosch, Berend-Jan

N1 - Funding Information: We thank Tony Smits for technical support. This study was done within the framework of the Utrecht Molecular Immunology Hub - Utrecht University and the research programme of the Netherlands Centre for One Health (www.ncoh.nl). Funding: The collaboration project is co-funded by the PPP Allowance made available by Health~Holland (Grant no. LSHM19136), Top Sector Life Sciences & Health, to stimulate public-private partnerships. Chunyan Wang was supported by a grant from the China Scholarship Council. T.M.S. and J.S. were funded by the Dutch Research Council NWO Gravitation 2013 BOO, Institute for Chemical Immunology (ICI; 024.002.009). Cryo-EM data processing was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative using grant no. EINF-398. Funding Information: We thank Tony Smits for technical support. This study was done within the framework of the Utrecht Molecular Immunology Hub - Utrecht University and the research programme of the Netherlands Centre for One Health ( www.ncoh.nl ). Funding: The collaboration project is co-funded by the PPP Allowance made available by Health~Holland (Grant no. LSHM19136), Top Sector Life Sciences & Health, to stimulate public-private partnerships. Chunyan Wang was supported by a grant from the China Scholarship Council. T.M.S. and J.S. were funded by the Dutch Research Council NWO Gravitation 2013 BOO, Institute for Chemical Immunology (ICI; 024.002.009). Cryo-EM data processing was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative using grant no. EINF-398. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Human coronavirus OC43 is a globally circulating common cold virus sustained by recurrent reinfections. How it persists in the population and defies existing herd immunity is unknown. Here we focus on viral glycoprotein S, the target for neutralizing antibodies, and provide an in-depth analysis of its antigenic structure. Neutralizing antibodies are directed to the sialoglycan-receptor binding site in S1 A domain, but, remarkably, also to S1 B. The latter block infection yet do not prevent sialoglycan binding. While two distinct neutralizing S1 B epitopes are readily accessible in the prefusion S trimer, other sites are occluded such that their accessibility must be subject to conformational changes in S during cell-entry. While non-neutralizing antibodies were broadly reactive against a collection of natural OC43 variants, neutralizing antibodies generally displayed restricted binding breadth. Our data provide a structure-based understanding of protective immunity and adaptive evolution for this endemic coronavirus which emerged in humans long before SARS-CoV-2.

AB - Human coronavirus OC43 is a globally circulating common cold virus sustained by recurrent reinfections. How it persists in the population and defies existing herd immunity is unknown. Here we focus on viral glycoprotein S, the target for neutralizing antibodies, and provide an in-depth analysis of its antigenic structure. Neutralizing antibodies are directed to the sialoglycan-receptor binding site in S1 A domain, but, remarkably, also to S1 B. The latter block infection yet do not prevent sialoglycan binding. While two distinct neutralizing S1 B epitopes are readily accessible in the prefusion S trimer, other sites are occluded such that their accessibility must be subject to conformational changes in S during cell-entry. While non-neutralizing antibodies were broadly reactive against a collection of natural OC43 variants, neutralizing antibodies generally displayed restricted binding breadth. Our data provide a structure-based understanding of protective immunity and adaptive evolution for this endemic coronavirus which emerged in humans long before SARS-CoV-2.

KW - Antibodies, Monoclonal

KW - Antibodies, Neutralizing

KW - Antibodies, Viral

KW - COVID-19

KW - Coronavirus OC43, Human/metabolism

KW - Epitopes

KW - Humans

KW - SARS-CoV-2

KW - Spike Glycoprotein, Coronavirus

UR - http://www.scopus.com/inward/record.url?scp=85130763834&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-30658-0

DO - 10.1038/s41467-022-30658-0

M3 - Article

C2 - 35614127

SN - 2041-1723

VL - 13

SP - 1

EP - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2921

ER -

Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this