Enhanced variant neutralization through glycan masking of SARS-CoV-2 XBB1.5 RBD
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.
Authors
- George Carnell (ORCID: https://orcid.org/0000-0001-8875-0989)
- Johannes Geiger
- Lorraine A. O’Reilly (ORCID: https://orcid.org/0000-0001-7134-6496)
- Christian Plank (ORCID: https://orcid.org/0000-0002-6072-4903)
- Diego Cantoni (ORCID: https://orcid.org/0000-0001-8527-7719)
- Jonathan Luke Heeney (ORCID: https://orcid.org/0000-0003-2702-1621)
- Rebecca Kinsley
- Sneha Vishwanath (ORCID: https://orcid.org/0000-0001-9960-547X)
- Joe Grove (ORCID: https://orcid.org/0000-0001-5390-7579)
- Chloe Qingzhou Huang (ORCID: https://orcid.org/0009-0009-1503-1030)
- Christian Dohmen (ORCID: https://orcid.org/0000-0001-9711-7982)
- Charlotte George (ORCID: https://orcid.org/0000-0002-6585-3288)
- Sheeba J. Sujit (ORCID: https://orcid.org/0000-0001-8302-7046)
- Nigel James Temperton (ORCID: https://orcid.org/0000-0002-7978-3815)
- Paul Tonks
- Ralf Wagner (ORCID: https://orcid.org/0000-0002-4226-6873)
- Verena Mummert
- Joey Olivier (ORCID: https://orcid.org/0000-0002-5144-5267)
- Anne Rosalind Samuel
- Martina Pfranger
Institutions
- University of Nottingham (GB)
- Medway School of Pharmacy (GB)
- University of Kent (GB)
- University of Cambridge (GB)
- Global Virus Network (US)
- University Hospital Regensburg (DE)
- Department of Virology (FR)
- Institute of Medical Microbiology and Hygiene (DE)
- MRC University of Glasgow Centre for Virus Research (GB)
- Ethris (Germany) (DE)
- Institute of Virology of the Slovak Academy of Sciences (SK)
- University of Greenwich (GB)
- University of Regensburg (DE)
- University of Glasgow (GB)
Publication Details
- Journal
- Emerging Microbes & Infections
- Published
- 2025-05-06
- DOI
- https://doi.org/10.1080/22221751.2025.2502011
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- UK Research and Innovation
- Coalition for Epidemic Preparedness Innovations
- Bayerisches Staatsministerium für Wissenschaft und Kunst
- Medical Research Council