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Enhanced variant neutralization through glycan masking of SARS-CoV-2 XBB1.5 RBD

Olivier, Joey, George, Charlotte, Huang, Chloe Qingzhou, Sujit, Sneha B., Tonks, Paul, Cantoni, Diego, Grove, Joe, O’Reilly, Laura, Geiger, Johannes, Dohmen, Christian, and others. (2025) Enhanced variant neutralization through glycan masking of SARS-CoV-2 XBB1.5 RBD. Emerging Microbes & Infections, 14 (1). Article Number 2502011. ISSN 2222-1751. (doi:10.1080/22221751.2025.2502011) (KAR id:110214)

Abstract

SARS-CoV-2 continues to evolve antigenically under the immune pressure exerted by both natural infection and vaccination. As new variants emerge, we face the recurring challenge of updating vaccines at significant financial cost to maintain their efficacy. To address this, novel strategies are needed to enhance the breadth of protection offered by vaccines or, at a minimum, extend their effectiveness over time. One such strategy is antigen modification. In this study, we introduce a glycosylation site into a binding but non-neutralizing epitope within the SARS-CoV-2 XBB.1.5 receptor binding domain (RBD) to redirect the immune response towards more potent neutralizing epitopes. Immunization of mice with this modified antigen via the mRNA vaccine platform resulted in a dramatic increase in neutralizing antibodies compared to the wild-type XBB.1.5 RBD, showing superior protection against a range of SARS-CoV-2 Omicron variants, from BA.2 to JN.1. Our findings reinforce the power of the glycan masking approach, which in combination with the now well-established mRNA vaccine platform can contribute to broader and better vaccines.

Item Type: Article
DOI/Identification number: 10.1080/22221751.2025.2502011
Uncontrolled keywords: SARS-CoV-2, Glycan masking, neutralising antibodies, next generation vaccines, receptor binding domain
Subjects: Q Science
R Medicine
Institutional Unit: Schools > Medway School of Pharmacy
Former Institutional Unit:
There are no former institutional units.
Funders: University of Kent (https://ror.org/00xkeyj56)
SWORD Depositor: JISC Publications Router
Depositing User: JISC Publications Router
Date Deposited: 23 Jul 2025 10:22 UTC
Last Modified: 23 Jul 2025 12:35 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/110214 (The current URI for this page, for reference purposes)

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