Frontiers in Immunology (Feb 2023)

Glycan masking of a non-neutralising epitope enhances neutralising antibodies targeting the RBD of SARS-CoV-2 and its variants

  • 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,
  • David Peterhoff,
  • Benedikt Asbach,
  • Volker Sandig,
  • Nigel Temperton,
  • Rebecca Kinsley,
  • Rebecca Kinsley,
  • Ralf Wagner,
  • Ralf Wagner,
  • Jonathan L. Heeney,
  • Jonathan L. Heeney

DOI
https://doi.org/10.3389/fimmu.2023.1118523
Journal volume & issue
Vol. 14

Abstract

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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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