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 journalArticleAcademicpeer-review

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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 S1A domain, but, remarkably, also to S1B. The latter block infection yet do not prevent sialoglycan binding. While two distinct neutralizing S1B 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 languageEnglish
Article number2921
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 25 May 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).

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