Carnell, George W. and Billmeier, Martina and Vishwanath, Sneha and Sans, Maria Suau and Wein, Hannah and George, Charlotte L. and Neckermann, Patrick and Del Rosario, Joanne Marie M. and Sampson, Alexander T. and Einhauser, Sebastian and Aguinam, Ernest T. and Ferrari, Matteo and Tonks, Paul and Nadesalingam, Angalee and Schuetz, Anja and Huang, Chloe Qingzhou and Wells, David A. and Paloniemi, Minna and Jordan, Ingo and Cantoni, Diego and Peterhoff, David and Asbach, Benedikt and Sandig, Volker and Temperton, Nigel and Kinsley, Rebecca and Wagner, Ralf and Heeney, Jonathan L. (2023) Glycan masking of a non-neutralising epitope enhances neutralising antibodies targeting the RBD of SARS-CoV-2 and its variants. FRONTIERS IN IMMUNOLOGY, 14: 1118523. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
The accelerated development of the first generation COVID-19 vaccines has saved millions of lives, and potentially more from the long-term sequelae of SARS-CoV-2 infection. The most successful vaccine candidates have used the full-length SARS-CoV-2 spike protein as an immunogen. As expected of RNA viruses, new variants have evolved and quickly replaced the original wild-type SARS-CoV-2, leading to escape from natural infection or vaccine induced immunity provided by the original SARS-CoV-2 spike sequence. Next generation vaccines that confer specific and targeted immunity to broadly neutralising epitopes on the SARS-CoV-2 spike protein against different variants of concern (VOC) offer an advance on current booster shots of previously used vaccines. Here, we present a targeted approach to elicit antibodies that neutralise both the ancestral SARS-CoV-2, and the VOCs, by introducing a specific glycosylation site on a non-neutralising epitope of the RBD. The addition of a specific glycosylation site in the RBD based vaccine candidate focused the immune response towards other broadly neutralising epitopes on the RBD. We further observed enhanced cross-neutralisation and cross-binding using a DNA-MVA CR19 prime-boost regime, thus demonstrating the superiority of the glycan engineered RBD vaccine candidate across two platforms and a promising candidate as a broad variant booster vaccine.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LENTIVIRAL VECTOR; CORONAVIRUSES; REPLICATION; ACE2; SARS-CoV-2 antibody; receptor binding domain (RBD); glycan masking; neutralising antibodies; pseudotype neutralisation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Mar 2024 14:40 |
| Last Modified: | 10 Mar 2024 14:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59605 |
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