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 Haperen, Sarah Townend, Frank J. M. Kuppeveld, Frank Grosveld, Neil A. Ranson, Joost Snijder, Raoul J. Groot, Daniel L. Hurdiss () and Berend-Jan Bosch ()
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Chunyan Wang: Utrecht University
Emma L. Hesketh: University of Leeds
Tatiana M. Shamorkina: Utrecht University
Wentao Li: Utrecht University
Peter J. Franken: Utrecht University
Dubravka Drabek: Erasmus Medical Center
Rien Haperen: Erasmus Medical Center
Sarah Townend: University of Leeds
Frank J. M. Kuppeveld: Utrecht University
Frank Grosveld: Erasmus Medical Center
Neil A. Ranson: University of Leeds
Joost Snijder: Utrecht University
Raoul J. Groot: Utrecht University
Daniel L. Hurdiss: Utrecht University
Berend-Jan Bosch: Utrecht University

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30658-0

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