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bioRxivBiochemistryPreprint

Analysis of SARS-CoV-2 spike glycosylation reveals shedding of a vaccine candidate

J. Brun, S. Vasiljevic, B. Gangadharan, M. Hensen, A. V. Chandran, M. L. Hill, J. L. Kiappes, R. A. Dwek, D. S. Alonzi, W. B. Struwe, N. Zitzmann

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Abstract

Severe acute respiratory syndrome coronavirus 2 is the causative pathogen of the COVID-19 pandemic which as of Nov 15, 2020 has claimed 1,319,946 lives worldwide. Vaccine development focuses on the viral trimeric spike glycoprotein as the main target of the humoral immune response. Viral spikes carry glycans that facilitate immune evasion by shielding specific protein epitopes from antibody neutralisation. Immunogen integrity is therefore important for glycoprotein-based vaccine candidates. Here we show how site-specific glycosylation differs between virus-derived spikes and spike proteins derived from a viral vectored SARS-CoV-2 vaccine candidate. We show that their distinctive cellular secretion pathways result in different protein glycosylation and secretion patterns, which may have implications for the resulting immune response and future vaccine design.

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