AUTHOR=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. TITLE=Glycan masking of a non-neutralising epitope enhances neutralising antibodies targeting the RBD of SARS-CoV-2 and its variants JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1118523 DOI=10.3389/fimmu.2023.1118523 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.