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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 ; Heeney, Jonathan L.

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.



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Details

Item typeArticle
Journal or Publication TitleFrontiers in Immunology
Publisher:FRONTIERS MEDIA SA
Place of Publication:LAUSANNE
Volume:14
Page Range:p. 1118523
Date23 February 2023
InstitutionsMedicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Identification Number
ValueType
10.3389/fimmu.2023.1118523DOI
KeywordsLENTIVIRAL VECTOR; CORONAVIRUSES; REPLICATION; ACE2; SARS-CoV-2 antibody; receptor binding domain (RBD); glycan masking; neutralising antibodies; pseudotype neutralisation
Dewey Decimal Classification600 Technology > 610 Medical sciences Medicine
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgYes
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-538974
Item ID53897

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