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Glycan masking of a non-neutralising epitope enhances neutralising antibodies targeting the RBD of SARS-CoV-2 and its variants
Carnell, George W.
, Billmeier, Martina, Vishwanath, Sneha
, Suau Sans, Maria, Wein, Hannah, George, Charlotte L., Neckermann, Patrick
, Del Rosario, Joanne Marie M.
, Sampson, Alexander T.
, Einhauser, Sebastian
, Aguinam, Ernest T.
, Ferrari, Matteo, Tonks, Paul, Nadesalingam, Angalee, Schütz, Anja, Huang, Chloe Qingzhou, Wells, David A.
, Paloniemi, Minna, Jordan, Ingo
, Cantoni, Diego
, Peterhoff, David
, Asbach, Benedikt, Sandig, Volker, Temperton, Nigel
, Kinsley, Rebecca, 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, p. 1118523.
Date of publication of this fulltext: 06 Mar 2023 15:32
Article
DOI to cite this document: 10.5283/epub.53897
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 ...
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.
Involved Institutions
Details
| Item type | Article | ||||
| Journal or Publication Title | Frontiers in Immunology | ||||
| Publisher: | FRONTIERS MEDIA SA | ||||
|---|---|---|---|---|---|
| Place of Publication: | LAUSANNE | ||||
| Volume: | 14 | ||||
| Page Range: | p. 1118523 | ||||
| Date | 23 February 2023 | ||||
| Institutions | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene | ||||
| Identification Number |
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| Keywords | LENTIVIRAL VECTOR; CORONAVIRUSES; REPLICATION; ACE2; SARS-CoV-2 antibody; receptor binding domain (RBD); glycan masking; neutralising antibodies; pseudotype neutralisation | ||||
| Dewey Decimal Classification | 600 Technology > 610 Medical sciences Medicine | ||||
| Status | Published | ||||
| Refereed | Yes, this version has been refereed | ||||
| Created at the University of Regensburg | Yes | ||||
| URN of the UB Regensburg | urn:nbn:de:bvb:355-epub-538974 | ||||
| Item ID | 53897 |
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