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 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.

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Item Type:	Article
Authors/Creators:	Wang, C Hesketh, EL https://orcid.org/0000-0002-4522-0061 Shamorkina, TM Li, W Franken, PJ Drabek, D van Haperen, R Townend, S van Kuppeveld, FJM Grosveld, F Ranson, NA https://orcid.org/0000-0002-3640-5275 Snijder, J de Groot, RJ Hurdiss, DL Bosch, B-J
Copyright, Publisher and Additional Information:	© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Published: December 2022 Published (online): 25 May 2022 Accepted: 9 May 2022
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Cryo EM, Image Processing (Leeds)
Depositing User:	Symplectic Publications
Date Deposited:	05 Jul 2022 13:32
Last Modified:	05 Jul 2022 13:32
Status:	Published
Publisher:	Nature Research
Identification Number:	10.1038/s41467-022-30658-0
Related URLs:	Author
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:188412

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

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