학술논문
Glycan masking of a non-neutralising epitope enhances neutralising antibodies targeting the RBD of SARS-CoV-2 and its variants
Document Type
article
Author
George W. Carnell; Martina Billmeier; Sneha Vishwanath; Maria Suau Sans; Hannah Wein; Charlotte L. George; Patrick Neckermann; Joanne Marie M. Del Rosario; Alexander T. Sampson; Sebastian Einhauser; Ernest T. Aguinam; Matteo Ferrari; Paul Tonks; Angalee Nadesalingam; Anja Schütz; Chloe Qingzhou Huang; David A. Wells; Minna Paloniemi; Ingo Jordan; Diego Cantoni; David Peterhoff; Benedikt Asbach; Volker Sandig; Nigel Temperton; Rebecca Kinsley; Ralf Wagner; Jonathan L. Heeney
Source
Frontiers in Immunology, Vol 14 (2023)
Subject
Language
English
ISSN
1664-3224
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.