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, and others. (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 . Article Number 1118523. ISSN 1664-3224. (doi:10.3389/fimmu.2023.1118523) (KAR id:100431)

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Official URL: https://doi.org/10.3389/fimmu.2023.1118523

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
DOI/Identification number:	10.3389/fimmu.2023.1118523
Uncontrolled keywords:	SARS-CoV-2 antibody, receptor binding domain (RBD), glycan masking, neutralising antibodies, pseudotype neutralisation
Subjects:	Q Science > QR Microbiology > QR355 Virology
Divisions:	Divisions > Division of Natural Sciences > Medway School of Pharmacy
Funders:	Wellcome Trust (https://ror.org/029chgv08)
Depositing User:	Nigel Temperton
Date Deposited:	11 Mar 2023 14:39 UTC
Last Modified:	13 Mar 2023 14:37 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/100431 (The current URI for this page, for reference purposes)

University of Kent Author Information

Temperton, Nigel.

Creator's ORCID:	https://orcid.org/0000-0002-7978-3815
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